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1. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author: Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., Loos, Ruth J. F., Turcot, Valerie, Lu, Yingchang, Highland, Heather M., Schurmann, Claudia, Justice, Anne E., Fine, Rebecca S., Bradfield, Jonathan P., Esko, Tonu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E., Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E., Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L., Alfred, Tamuno, Feitosa, Mary F., Masca, Nicholas G. D., Manning, Alisa K., Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C. Y., Reiner, Alex P., Vedantam, Sailaja, Willems, Sara M., Winkler, Thomas W., Abecasis, Goncalo, Aben, Katja K., Alam, Dewan S., Alharthi, Sameer E., Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Bang, Lia E., Barroso, Ines, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Brumat, Marco, Burt, Amber A., Butterworth, Adam S., Campbell, Peter T., Cappellani, Stefania, Carey, David J., Catamo, Eulalia, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der I., Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Crosslin, David S., Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I. W., Groot, Mark C. H., Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Heijer, Martin, Hollander, Anneke I., Ruijter, Hester M., Dennis, Joe G., Denny, Josh C., Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Edwards, Todd L., Ellinghaus, David, Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I. Sadaf, Faul, Jessica D., Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Franke, Andre, Franks, Paul W., Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P., Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Joergen, Grant, Struan F. A., Grarup, Niels, Griffiths, Helen L., Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R., Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Have, Christian T., Hayward, Caroline, He, Liang, Heard-Costa, Nancy L., Heath, Andrew C., Heid, Iris M., Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Huang, Paul L., Huffman, Jennifer E., Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jia, Yucheng, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A., Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltan, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Liu, Yongmei, Lo, Ken S., Lophatananon, Artitaya, Lotery, Andrew J., Loukola, Anu, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mannisto, Satu, Marenne, Gaelle, Mazul, Angela L., McCarthy, Mark I., McKean-Cowdin, Roberta, Medland, Sarah E., Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L., Moilanen, Leena, Moitry, Marie, Montgomery, Grant W., Mook-Kanamori, Dennis O., Moore, Carmel, Mori, Trevor A., Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Nyholt, Dale R., O'Connel, Jeffrey R., O'Donoghue, Michelle L., Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Palmer, Nicholette D., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Pers, Tune H., Person, Thomas N., Peters, Annette, Petersen, Eva R. B., Peyser, Patricia A., Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J., Puolijoki, Hannu, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Renström, Frida, Rheinberger, Myriam, Ridker, Paul M., Rioux, John D., Rivas, Manuel A., Roberts, David J., Robertson, Neil R., Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati H., Sheu, Wayne H. -H., Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Albert V., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J., Tada, Hayato, Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Uusitupa, Matti, Laan, Sander W., Duijn, Cornelia M., Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Voelker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Ware, Erin B., Wareham, Nicholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Witte, Daniel R., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T., Rotter, Jerome I., Pospisilik, John A., Rivadeneira, Fernando, Borecki, Ingrid B., Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, North, Kari E., Lindgren, Cecilia M., Hirschhorn, Joel N., and Loos, Ruth J. F.
Abstract: Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity., Corrections:Turcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 50, 765–766 (2018). DOI: 10.1038/s41588-018-0050-yTurcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 50, 766–767 (2018). DOI: 10.1038/s41588-018-0082-3Turcot, V., Lu, Y., Highland, H.M. et al. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 51, 1191–1192 (2019). DOI: 10.1038/s41588-019-0447-2
Published: 2018
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2. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Author: Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., Chasman, Daniel I., Sung, Yun J., Winkler, Thomas W., de las Fuentes, Lisa, Bentley, Amy R., Brown, Michael R., Kraja, Aldi T., Schwander, Karen, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Kilpelainen, Tuomas O., Richard, Melissa A., Noordam, Raymond, Aslibekyan, Stella, Aschard, Hugues, Bartz, Traci M., Dorajoo, Rajkumar, Liu, Yongmei, Manning, Alisa K., Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Warren, Helen R., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando Pires, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kahonen, Mika, Kasturiratne, Anuradhani, Kuhnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian' an, McKenzie, Colin A., Meian, He, Nelson, Christopher P., Rauramaa, Rainer, Schupf, Nicole, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van der Most, Peter J., Varga, Tibor V., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan, Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cabrera, Claudia P., Cade, Brian, Caizheng, Yu, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Chauhan, Ganesh, Christensen, Kaare, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Debette, Stephanie, Dorr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Fisher, Virginia A., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Graff, Misa, Gu, C. Charles, Gu, Dongfeng, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hofman, Albert, Howard, Barbara V., Hunt, Steven, Irvin, Marguerite R., Jia, Yucheng, Joehanes, Roby, Justice, Anne E., Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Komulainen, Pirjo, Kooperberg, Charles, Krieger, Jose E., Kubo, Michiaki, Kuusisto, Johanna, Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Kiang, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Long, Jirong, Louie, Tin, Magi, Reedik, Mahajan, Anubha, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Morris, Andrew P., Mosley, Thomas H., Jr., Munson, Peter, Murray, Alison D., Nalls, Mike A., Nasri, Ubaydah, Norris, Jill M., North, Kari, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Seshadri, Sudha, Sever, Peter, Sitlani, Colleen M., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Ultterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya X., Bin Wei, Wen, Williams, Christine, Wilson, Gregory, Wojczynski, Mary K., Yao, Jie, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost B., Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Newman, Anne B., Oldehinkel, Albertine J., Pereira, Alexandre C., Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Wu, Tangchun, Zheng, Wei, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Kardia, Sharon L. R., Kritchevsky, Stephen B., Levy, Daniel, O'Connell, Jeff R., Psaty, Bruce M., van Dam, Rob M., Sims, Mario, Arnett, Donna K., Mook-Kanamori, Dennis O., Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, Fornage, Myriam, Rotimi, Charles N., Province, Michael A., van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotter, Jerome I., Zhu, Xiaofeng, Bierut, Laura J., Gauderman, W. James, Caulfield, Mark J., Elliott, Paul, Rice, Kenneth, Munroe, Patricia B., Morrison, Alanna C., Cupples, L. Adrienne, Rao, Dabeeru C., and Chasman, Daniel I.
Abstract: Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).
Published: 2018
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3. Rare and low-frequency coding variants alter human adult height

Author: Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rueger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valerie, Young, Kristin L., Winkler, Thomas W., Esko, Tonu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bonnycastle, Lori L., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul I. W., de Borst, Gert J., de Denus, Simon, de Groot, Mark C. H., de Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkila, Kauko, Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Kury, Sebastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I-Te, Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L., Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Ntalla, Ioanna, O'Connel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renstrom, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, t Hart, Leen M., Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Ulivi, Sheila, van der Laan, Sander W., Van Der Leij, Andries R., van Duijn, Cornelia M., van Schoor, Natasja M., van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I., Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard-Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Claus, Kutalik, Zoltan, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Panos, Lettre, Guillaume, Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rueger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valerie, Young, Kristin L., Winkler, Thomas W., Esko, Tonu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bonnycastle, Lori L., Bork-Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J., Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul I. W., de Borst, Gert J., de Denus, Simon, de Groot, Mark C. H., de Mutsert, Renee, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke-Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkila, Kauko, Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan-Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jorgensen, Marit E., Jorgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, Rene S., Kahonen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Kury, Sebastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I-Te, Lehtimaki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A., Lyytikainen, Leo-Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L., Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njolstad, Pal R., Nordestgaard, Borge G., Ntalla, Ioanna, O'Connel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Markus, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renstrom, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, t Hart, Leen M., Tansey, Katherine E., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, Andre G., Ulivi, Sheila, van der Laan, Sander W., Van Der Leij, Andries R., van Duijn, Cornelia M., van Schoor, Natasja M., van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Edwards, Digna R. Velez, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I., Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard-Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Claus, Kutalik, Zoltan, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Panos, and Lettre, Guillaume
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2017
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4. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Author: Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, Franks, Paul W., Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, and Franks, Paul W.
Abstract: Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Published: 2017
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5. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017
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6. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author: Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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7. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017
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8. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author: Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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9. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Author: Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, Franks, Paul W., Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, and Franks, Paul W.
Abstract: Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Published: 2017
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10. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Author: Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, Franks, Paul W., Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, and Franks, Paul W.
Abstract: Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Published: 2017
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11. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017
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12. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author: Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
Full Text: View/download PDF

13. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author: Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
Full Text: View/download PDF

14. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Author: Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, Franks, Paul W., Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, and Franks, Paul W.
Abstract: Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Published: 2017
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15. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017
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16. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Author: Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, Franks, Paul W., Shungin, Dmitry, Deng, Wei Q., Varga, Tibor V., Luan, Jian'an, Mihailov, Evelin, Metspalu, Andres, Morris, Andrew P., Forouhi, Nita G., Lindgren, Cecilia, Magnusson, Patrik K. E., Pedersen, Nancy L., Hallmans, Göran, Chu, Audrey Y., Justice, Anne E., Graff, Mariaelisa, Winkler, Thomas W., Rose, Lynda M., Langenberg, Claudia, Cupples, L. Adrienne, Ridker, Paul M., Wareham, Nicholas J., Ong, Ken K., Loos, Ruth J. F., Chasman, Daniel I., Ingelsson, Erik, Kilpeläinen, Tuomas O., Scott, Robert A., Mägi, Reedik, Paré, Guillaume, and Franks, Paul W.
Abstract: Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
Published: 2017
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17. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Author: Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., Kilpelainen, Tuomas O., Graff, Mariaelisa, Scott, Robert A., Justice, Anne E., Young, Kristin L., Feitosa, Mary F., Barata, Llilda, Winkler, Thomas W., Chu, Audrey Y., Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L., den Hoed, Marcel, Ahluwalia, Tarunveer S., Qi, Qibin, Ngwa, Julius S., Renström, Frida, Quaye, Lydia, Eicher, John D., Hayes, James E., Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E., Zhang, Weihua, Zhao, Wei, Griffin, Paula J., Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M., Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E., Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V., Whitfield, John B., Zhao, Jing Hua, Stringham, Heather M., Lyytikainen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J., Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F., Cadby, Gemma, Tanaka, Toshiko, Magl, Reedlk, Van der Most, Peter J., Jackson, Anne U., Bragg-Gresham, Jennifer L., Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Asa, Snitker, Soren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S., Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N., Bergmann, Sven, Bertoni, Alain G., Blangero, John, Bonnefond, Amelle, Bonnycastle, Lori L., Borja, Judith B., Brage, Soren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S., Collins, Francis S., Corre, Tanguy, Smith, George Davey, Delgado, Graciela E., Dueker, Nicole, Doerr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tonu, Faul, Jessica D., Fu, Mao, Faerch, Kristine, Gieger, Christian, Glaeser, Sven, Gong, Jian, Gordon-Larsen, Penny, Grallert, Harald, Grammer, Tanja B., Grarup, Niels, van Grootheest, Gerard, Harald, Kennet, Hastie, Nicholas D., Havulinna, Aki S., Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J., Holmens, Oddgeir L., Holzapfel, Christina, Hottenga, Jouke Jan, Huang, Jie, Huang, Tao, Hui, Jennie, Huth, Cornelia, Hutri-Kahonen, Nina, James, Alan L., Jansson, John-Olov, Jhun, Min A., Juonala, Markus, Kinnunen, Leena, Koistinen, Heikki A., Kolcic, Ivana, Komulainen, Pirjo, Kuusisto, Johanna, Kvaloy, Kirsti, Kahonen, Mika, Lakka, Timo A., Launer, Lenore J., Lehne, Benjamin, Lindgren, Cecilia M., Lorentzon, Mattias, Luben, Robert, Marre, Michel, Milaneschi, Yuri, Monda, Keri L., Montgomery, Grant W., De Moor, Marleen H. M., Mulas, Antonella, Mueller-Nurasyid, Martina, Musk, A. W., Mannikko, Reija, Mannisto, Satu, Narisu, Narisu, Nauck, Matthias, Nettleton, Jennifer A., Nolte, Ilja M., Oldehinkel, Albertine J., Olden, Matthias, Ong, Ken K., Padmanabhan, Sandosh, Paternoster, Lavinia, Perez, Jeremiah, Perola, Markus, Peters, Annette, Peters, Ulrike, Peyser, Patricia A., Prokopenko, Inga, Puolijoki, Hannu, Raitakari, Olli T., Rankinen, Tuomo, Rasmussen-Torvik, Laura J., Rawal, Rajesh, Ridker, Paul M., Rose, Lynda M., Rudan, Igor, Sarti, Cinzia, Sarzynski, Mark A., Savonen, Kai, Scott, William R., Sanna, Serena, Shuldiner, Alan R., Sidney, Steve, Silbernagel, Guenther, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Stancakova, Alena, Sternfeld, Barbara, Swift, Amy J., Tammelin, Tuija, Tan, Sian-Tsung, Thorand, Barbara, Thuillier, Dorothee, Vandenput, Liesbeth, Vestergaard, Henrik, van Vliet-Ostaptchouk, Jana V., Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Walker, Mark, Wild, Sarah, Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Zubair, Niha, Haiman, Christopher A., Lemarchand, Loic, Gyllensten, Ulf, Ohlsson, Claes, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G., Perusse, Louis, Wilson, James F., Hayward, Caroline, Polasek, Ozren, Cucca, Francesco, Hveem, Kristian, Hartman, Catharina A., Toenjes, Anke, Bandinelli, Stefania, Palmer, Lyle J., Kardia, Sharon L. R., Rauramaa, Rainer, Sorensen, Thorkild I. A., Tuomilehto, Jaakko, Salomaa, Veikko, Penninx, Brenda W. J. H., de Geus, Eco J. C., Boomsma, Dorret I., Lehtimaki, Terho, Mangino, Massimo, Laakso, Markku, Bouchard, Claude, Martin, Nicholas G., Kuh, Diana, Liu, Yongmei, Linneberg, Allan, Maerz, Winfried, Strauch, Konstantin, Kivimaki, Mika, Harris, Tamara B., Gudnason, Vilmundur, Voelzke, Henry, Qi, Lu, Jarvelin, Marjo-Riitta, Chambers, John C., Kooner, Jaspal S., Froguel, Philippe, Kooperberg, Charles, Vollenweider, Peter, Hallmans, Göran, Hansen, Torben, Pedersen, Oluf, Metspalu, Andres, Wareham, Nicholas J., Langenberg, Claudia, Weir, David R., Porteous, David J., Boerwinkle, Eric, Chasman, Daniel I., Abecasis, Goncalo R., Barroso, Ines, McCarthy, Mark I., Frayling, Timothy M., O'Connell, Jeffrey R., van Duijn, Cornelia M., Boehnke, Michael, Heid, Iris M., Mohlke, Karen L., Strachan, David P., Fox, Caroline S., Liu, Ching-Ti, Hirschhorn, Joel N., Klein, Robert J., Johnson, Andrew D., Borecki, Ingrid B., Franks, Paul W., North, Kari E., Cupples, L. Adrienne, Loos, Ruth J. F., and Kilpelainen, Tuomas O.
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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18. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, Cupples, L Adrienne, Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David, Ngwa, Julius S, Ahluwalia, Tarunveer S, Chu, Audrey Y, Heard-Costa, Nancy L, Lim, Elise, Perez, Jeremiah, Eicher, John D, Kutalik, Zoltan, Xue, Luting, Mahajan, Anubha, Renström, Frida, Wu, Joseph, Qi, Qibin, Ahmad, Shafqat, Alfred, Tamuno, Amin, Najaf, Bielak, Lawrence F, Bonnefond, Amelie, Bragg, Jennifer, Cadby, Gemma, Chittani, Martina, Coggeshall, Scott, Corre, Tanguy, Direk, Nese, Eriksson, Joel, Fischer, Krista, Gorski, Mathias, Neergaard Harder, Marie, Horikoshi, Momoko, Huang, Tao, Huffman, Jennifer E, Jackson, Anne U, Justesen, Johanne Marie, Kanoni, Stavroula, Kinnunen, Leena, Kleber, Marcus E, Komulainen, Pirjo, Kumari, Meena, Lim, Unhee, Luan, Jian'an, Lyytikainen, Leo-Pekka, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Middelberg, Rita P S, Muller-Nurasyid, Martina, Navarro, Pau, Perusse, Louis, Pervjakova, Natalia, Sarti, Cinzia, Smith, Albert Vernon, Smith, Jennifer A, Stancakova, Alena, Strawbridge, Rona J, Stringham, Heather M, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van der Most, Peter J, Van Vliet-Ostaptchouk, Jana V, Vedantam, Sailaja L, Verweij, Niek, Vink, Jacqueline M, Vitart, Veronique, Wu, Ying, Yengo, Loic, Zhang, Weihua, Hua Zhao, Jing, Zimmermann, Martina E, Zubair, Niha, Abecasis, Goncalo R, Adair, Linda S, Afaq, Saima, Afzal, Uzma, Bakker, Stephan J L, Bartz, Traci M, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L, Bottinger, Erwin, Braga, Daniele, Buckley, Brendan M, Buyske, Steve, Campbell, Harry, Chambers, John C, Collins, Francis S, Curran, Joanne E, de Borst, Gert J, de Craen, Anton J M, de Geus, Eco J C, Dedoussis, George, Delgado, Graciela E, den Ruijter, Hester M, Eiriksdottir, Gudny, Eriksson, Anna L, Esko, Tonu, Faul, Jessica D, Ford, Ian, Forrester, Terrence, Gertow, Karl, Gigante, Bruna, Glorioso, Nicola, Gong, Jian, Grallert, Harald, Grammer, Tanja B, Grarup, Niels, Haitjema, Saskia, Hallmans, Göran, Hamsten, Anders, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas D, Heath, Andrew C, Hernandez, Dena, Hindorff, Lucia, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Homuth, Georg, Jan Hottenga, Jouke, Huang, Jie, Hung, Joseph, Hutri-Kahonen, Nina, Ingelsson, Erik, James, Alan L, Jansson, John-Olov, Jarvelin, Marjo-Riitta, Jhun, Min A, Jorgensen, Marit E, Juonala, Markus, Kahonen, Mika, Karlsson, Magnus, Koistinen, Heikki A, Kolcic, Ivana, Kolovou, Genovefa, Kooperberg, Charles, Kramer, Bernhard K, Kuusisto, Johanna, Kvaloy, Kirsti, Lakka, Timo A, Langenberg, Claudia, Launer, Lenore J, Leander, Karin, Lee, Nanette R, Lind, Lars, Lindgren, Cecilia M, Linneberg, Allan, Lobbens, Stephane, Loh, Marie, Lorentzon, Mattias, Luben, Robert, Lubke, Gitta, Ludolph-Donislawski, Anja, Lupoli, Sara, Madden, Pamela A F, Mannikko, Reija, Marques-Vidal, Pedro, Martin, Nicholas G, McKenzie, Colin A, McKnight, Barbara, Mellstrom, Dan, Menni, Cristina, Montgomery, Grant W, Musk, Aw Bill, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Oldehinkel, Albertine J, Olden, Matthias, Ong, Ken K, Padmanabhan, Sandosh, Peyser, Patricia A, Pisinger, Charlotta, Porteous, David J, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rasmussen-Torvik, Laura J, Rawal, Rajesh, Rice, Treva, Ridker, Paul M, Rose, Lynda M, Bien, Stephanie A, Rudan, Igor, Sanna, Serena, Sarzynski, Mark A, Sattar, Naveed, Savonen, Kai, Schlessinger, David, Scholtens, Salome, Schurmann, Claudia, Scott, Robert A, Sennblad, Bengt, Siemelink, Marten A, Silbernagel, Gunther, Slagboom, P Eline, Snieder, Harold, Staessen, Jan A, Stott, David J, Swertz, Morris A, Swift, Amy J, Taylor, Kent D, Tayo, Bamidele O, Thorand, Barbara, Thuillier, Dorothee, Tuomilehto, Jaakko, Uitterlinden, Andre G, Vandenput, Liesbeth, Vohl, Marie-Claude, Volzke, Henry, Vonk, Judith M, Waeber, Gerard, Waldenberger, Melanie, Westendorp, R G J, Wild, Sarah, Willemsen, Gonneke, Wolffenbuttel, Bruce H R, Wong, Andrew, Wright, Alan F, Zhao, Wei, Zillikens, M Carola, Baldassarre, Damiano, Balkau, Beverley, Bandinelli, Stefania, Boger, Carsten A, Boomsma, Dorret I, Bouchard, Claude, Bruinenberg, Marcel, Chasman, Daniel I, Chen, Yii-DerIda, Chines, Peter S, Cooper, Richard S, Cucca, Francesco, Cusi, Daniele, Faire, Ulf de, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Gordon-Larsen, Penny, Grabe, Hans-Jorgen, Gudnason, Vilmundur, Haiman, Christopher A, Hayward, Caroline, Hveem, Kristian, Johnson, Andrew D, Wouter Jukema, J, Kardia, Sharon L R, Kivimaki, Mika, Kooner, Jaspal S, Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Marchand, Loic Le, Marz, Winfried, McCarthy, Mark I, Metspalu, Andres, Morris, Andrew P, Ohlsson, Claes, Palmer, Lyle J, Pasterkamp, Gerard, Pedersen, Oluf, Peters, Annette, Peters, Ulrike, Polasek, Ozren, Psaty, Bruce M, Qi, Lu, Rauramaa, Rainer, Smith, Blair H, Sorensen, Thorkild I A, Strauch, Konstantin, Tiemeier, Henning, Tremoli, Elena, van der Harst, Pim, Vestergaard, Henrik, Vollenweider, Peter, Wareham, Nicholas J, Weir, David R, Whitfield, John B, Wilson, James F, Tyrrell, Jessica, Frayling, Timothy M, Barroso, Ines, Boehnke, Michael, Deloukas, Panagiotis, Fox, Caroline S, Hirschhorn, Joel N, Hunter, David J, Spector, Tim D, Strachan, David P, van Duijn, Cornelia M, Heid, Iris M, Mohlke, Karen L, Marchini, Jonathan, Loos, Ruth J F, Kilpelainen, Tuomas O, Liu, Ching-Ti, Borecki, Ingrid B, North, Kari E, and Cupples, L Adrienne
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017
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19. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltan, Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Zhao, Jing Hua, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Asa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stancakova, Alena, Strawbridge, Rona J., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Settee, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loic, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blueher, Matthias, Bohringer, Stefan, Bonnycastle, Lori L., Boettcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Chen, Yii-Der Ida, Clarke, Robert, Daw, E. Warwick, de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Joergen, Grallert, Harald, Grammer, Tanja B., Graessler, Jurgen, Gronberg, Henrik, Groves, Christopher J., Gusto, Gaeelle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Qinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Asa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lo, Ken Sin, Lobbens, Stephane, Lorbeer, Roberto, Lu, Yingchang, Mach, Francois, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Noethen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wrightl, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gadin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, van 't Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Cupples, L. Adrienne, Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrieres, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Hovingh, G. Kees, Humphries, Steve E., Hunt, Steven C., Hypponen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Joeckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Laic, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramines, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Toenjes, Anke, Tregouet, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Willemsen, Gonneke, Witteman, Jacqueline C., Zillikens, M. Carola, Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stephane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. 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Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnu R., Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., O'Connell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijri, Cornelia M., Abecasis, Goncalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, Andre, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Ines, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., Speliotes, Elizabeth K., Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltan, Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Zhao, Jing Hua, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Asa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stancakova, Alena, Strawbridge, Rona J., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Settee, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loic, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blueher, Matthias, Bohringer, Stefan, Bonnycastle, Lori L., Boettcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Chen, Yii-Der Ida, Clarke, Robert, Daw, E. 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Abstract: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015
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20. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Lockes, Adam E., Maegi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltan, Luan, Jian'an, Randall, Joshua C., Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivaniss, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stancakova, Alena, Sung, Yun Ju, Tanakam, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loic, Zhang, Weihua, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blueher, Matthias, Buhringer, Stefan, Bonnet, Fabrice, Boettcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Daw, E. Warwick, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrichs, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Graessler, Juergen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkila, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lobbens, Stephane, Lorentzon, Mattias, Mach, Francois, Magnusson, Patrik K. 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W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltan, Luan, Jian'an, Randall, Joshua C., Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivaniss, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stancakova, Alena, Sung, Yun Ju, Tanakam, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loic, Zhang, Weihua, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blueher, Matthias, Buhringer, Stefan, Bonnet, Fabrice, Boettcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Daw, E. 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E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Ken L., Mooijaart, Simon P., Muehleisen, Thomas W., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Smith, Albert Vernon, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. 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Carola, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Ines, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., and Mohlke, Karen L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015
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21. Defining the role of common variation in the genomic and biological architecture of adult human height

Author: Wood, Andrew R, Esko, Tonu, Yang, Jian, Vedantam, Sailaja, Pers, Tune H, Gustafsson, Stefan, Chu, Audrey Y, Estrada, Karol, Luan, Jian'an, Kutalik, Zoltán, Amin, Najaf, Buchkovich, Martin L, Croteau-Chonka, Damien C, Day, Felix R, Duan, Yanan, Fall, Tove, Fehrmann, Rudolf, Ferreira, Teresa, Jackson, Anne U, Karjalainen, Juha, Lo, Ken Sin, Locke, Adam E, Mägi, Reedik, Mihailov, Evelin, Porcu, Eleonora, Randall, Joshua C, Scherag, André, Vinkhuyzen, Anna A E, Westra, Harm-Jan, Winkler, Thomas W, Workalemahu, Tsegaselassie, Zhao, Jing Hua, Absher, Devin, Albrecht, Eva, Anderson, Denise, Baron, Jeffrey, Beekman, Marian, Demirkan, Ayse, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Fraser, Ross M, Goel, Anuj, Gong, Jian, Justice, Anne E, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Lui, Julian C, Mangino, Massimo, Mateo Leach, Irene, Medina-Gomez, Carolina, Nalls, Michael A, Nyholt, Dale R, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Prokopenko, Inga, Ried, Janina S, Ripke, Stephan, Shungin, Dmitry, Stancáková, Alena, Strawbridge, Rona J, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Afzal, Uzma, Arnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Bolton, Jennifer L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Buckley, Brendan M, Buyske, Steven, Caspersen, Ida H, Chines, Peter S, Clarke, Robert, Claudi-Boehm, Simone, Cooper, Matthew, Daw, E Warwick, De Jong, Pim A, Deelen, Joris, Delgado, Graciela, Denny, Josh C, Dhonukshe-Rutten, Rosalie, Dimitriou, Maria, Doney, Alex S F, Dörr, Marcus, Eklund, Niina, Eury, Elodie, Folkersen, Lasse, Garcia, Melissa E, Geller, Frank, Giedraitis, Vilmantas, Go, Alan S, Grallert, Harald, Grammer, Tanja B, 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Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Nöthen, Markus M, Oozageer, Laticia, Pilz, Stefan, Rayner, Nigel W, Renström, Frida, Robertson, Neil R, Rose, Lynda M, Roussel, Ronan, Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R, Schunkert, Heribert, Scott, Robert A, Sehmi, Joban, Seufferlein, Thomas, Shi, Jianxin, Silventoinen, Karri, Smit, Johannes H, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V, Stirrups, Kathleen, Stott, David J, Stringham, Heather M, Sundström, Johan, Swertz, Morris A, Syvänen, Ann-Christine, Tayo, Bamidele O, Thorleifsson, Gudmar, Tyrer, Jonathan P, van Dijk, Suzanne, van Schoor, Natasja M, van der Velde, Nathalie, van Heemst, Diana, van Oort, Floor V A, Vermeulen, Sita H, Verweij, Niek, Vonk, Judith M, Waite, Lindsay L, Waldenberger, Melanie, Wennauer, Roman, Wilkens, Lynne R, Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K, Wong, Andrew, Wright, Alan F, Zhang, Qunyuan, Arveiler, Dominique, Bakker, Stephan J L, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boomsma, Dorret I, Bornstein, Stefan R, Bovet, Pascal, Brambilla, Paolo, Brown, Morris J, Campbell, Harry, Caulfield, Mark J, Chakravarti, Aravinda, Collins, Rory, Collins, Francis S, Crawford, Dana C, Cupples, L Adrienne, Danesh, John, de Faire, Ulf, den Ruijter, Hester M, Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G, Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G, Forrester, Terrence, Gansevoort, Ron T, Gejman, Pablo V, Gieger, Christian, Golay, Alain, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Haas, David W, Hall, Alistair S, Harris, Tamara B, Hattersley, Andrew T, Heath, Andrew C, Hengstenberg, Christian, Hicks, Andrew A, Hindorff, Lucia A, Hingorani, Aroon D, Hofman, Albert, Hovingh, G Kees, Humphries, Steve E, Hunt, Steven C, Hypponen, Elina, Jacobs, Kevin B, Jarvelin, Marjo-Riitta, Jousilahti, Pekka, Jula, Antti M, Kaprio, Jaakko, Kastelein, John J P, Kayser, Manfred, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M, Kiemeney, Lambertus A, Kooner, Jaspal S, Kooperberg, Charles, Koskinen, Seppo, Kovacs, Peter, Kraja, Aldi T, Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A, Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lupoli, Sara, Madden, Pamela A F, Männistö, Satu, Manunta, Paolo, Marette, André, Matise, Tara C, McKnight, Barbara, Meitinger, Thomas, Moll, Frans L, Montgomery, Grant W, Morris, Andrew D, Morris, Andrew P, Murray, Jeffrey C, Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J, Ong, Ken K, Ouwehand, Willem H, Pasterkamp, Gerard, Peters, Annette, Pramstaller, Peter P, Price, Jackie F, Qi, Lu, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Ritchie, Marylyn, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Saramies, Jouko, Sarzynski, Mark A, Schwarz, Peter E H, Sebert, Sylvain, Sever, Peter, Shuldiner, Alan R, Sinisalo, Juha, Steinthorsdottir, Valgerdur, Stolk, Ronald P, Tardif, Jean-Claude, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Amouyel, Philippe, Asselbergs, Folkert W, Assimes, Themistocles L, Bochud, Murielle, Boehm, Bernhard O, Boerwinkle, Eric, Bottinger, Erwin P, Bouchard, Claude, Cauchi, Stéphane, Chambers, John C, Chanock, Stephen J, Cooper, Richard S, de Bakker, Paul I W, Dedoussis, George, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Groop, Leif C, Haiman, Christopher A, Hamsten, Anders, Hayes, M Geoffrey, Hui, Jennie, Hunter, David J, Hveem, Kristian, Jukema, J Wouter, Kaplan, Robert C, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G, März, Winfried, Melbye, Mads, Moebus, Susanne, Munroe, Patricia B, Njølstad, Inger, Oostra, Ben A, Palmer, Colin N A, Pedersen, Nancy L, Perola, Markus, Pérusse, Louis, Peters, Ulrike, Powell, Joseph E, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Reinmaa, Eva, Ridker, Paul M, Rivadeneira, Fernando, Rotter, Jerome I, Saaristo, Timo E, Saleheen, Danish, Schlessinger, David, Slagboom, P Eline, Snieder, Harold, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Tuomilehto, Jaakko, Uusitupa, Matti, van der Harst, Pim, Völzke, Henry, Walker, Mark, Wareham, Nicholas J, Watkins, Hugh, Wichmann, H-Erich, Wilson, James F, Zanen, Pieter, Deloukas, Panos, Heid, Iris M, Lindgren, Cecilia M, Mohlke, Karen L, Speliotes, Elizabeth K, Thorsteinsdottir, Unnur, Barroso, Inês, Fox, Caroline S, North, Kari E, Strachan, David P, Beckmann, Jacques S, Berndt, Sonja I, Boehnke, Michael, Borecki, Ingrid B, McCarthy, Mark I, Metspalu, Andres, Stefansson, Kari, Uitterlinden, André G, van Duijn, Cornelia M, Franke, Lude, Willer, Cristen J, Price, Alkes L, Lettre, Guillaume, Loos, Ruth J F, Weedon, Michael N, Ingelsson, Erik, O'Connell, Jeffrey R, Abecasis, Goncalo R, Chasman, Daniel I, Goddard, Michael E, Visscher, Peter M, Hirschhorn, Joel N, and Frayling, Timothy M
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Published: 2014
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22. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Author: Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, Heid, Iris M, Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, and Heid, Iris M
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Published: 2013
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23. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Author: Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, Heid, Iris M, Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, and Heid, Iris M
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Published: 2013
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24. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Berndt, Sonja I., Gustafsson, Stefan, Maegi, Reedik, Ganna, Andrea, Wheeler, Eleanor, Feitosa, Mary F., Justice, Anne E., Monda, Keri L., Croteau-Chonka, Damien C., Day, Felix R., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gentilini, Davide, Jackson, Anne U., Luan, Jian'an, Randall, Joshua C., Vedantam, Sailaja, Willer, Cristen J., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Hu, Yi-Juan, Lee, Sang Hong, Liang, Liming, Lin, Dan-Yu, Min, Josine L., Neale, Benjamin M., Thorleifsson, Gudmar, Yang, Jian, Albrecht, Eva, Amin, Najaf, Bragg-Gresham, Jennifer L., Cadby, Gemma, den Heijer, Martin, Eklund, Niina, Fischer, Krista, Goel, Anuj, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jarick, Ivonne, Johansson, Asa, Johnson, Toby, Kanoni, Stavroula, Kleber, Marcus E., Koenig, Inke R., Kristiansson, Kati, Kutalik, Zoltn, Lamina, Claudia, Lecoeur, Cecile, Li, Guo, Mangino, Massimo, McArdle, Wendy L., Medina-Gomez, Carolina, Mueller-Nurasyid, Martina, Ngwa, Julius S., Nolte, Ilja M., Paternoster, Lavinia, Pechlivanis, Sonali, Perola, Markus, Peters, Marjolein J., Preuss, Michael, Rose, Lynda M., Shi, Jianxin, Shungin, Dmitry, Smith, Albert Vernon, Strawbridge, Rona J., Surakka, Ida, Teumer, Alexander, Trip, Mieke D., Tyrer, Jonathan, Van Vliet-Ostaptchouk, Jana V., Vandenput, Liesbeth, Waite, Lindsay L., Zhao, Jing Hua, Absher, Devin, Asselbergs, Folkert W., Atalay, Mustafa, Attwood, Antony P., Balmforth, Anthony J., Basart, Hanneke, Beilby, John, Bonnycastle, Lori L., Brambilla, Paolo, Bruinenberg, Marcel, Campbell, Harry, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Connell, John M., Cookson, William O., de Faire, Ulf, de Vegt, Femmie, Dei, Mariano, Dimitriou, Maria, Edkins, Sarah, Estrada, Karol, Evans, David M., Farrall, Martin, Ferrario, Marco M., Ferrieres, Jean, Franke, Lude, Frau, Francesca, Gejman, Pablo V., Grallert, Harald, Groenberg, Henrik, Gudnason, Vilmundur, Hall, Alistair S., Hall, Per, Hartikainen, Anna-Liisa, Hayward, Caroline, Heard-Costa, Nancy L., Heath, Andrew C., Hebebrand, Johannes, Homuth, Georg, Hu, Frank B., Hunt, Sarah E., Hyppoenen, Elina, Iribarren, Carlos, Jacobs, Kevin B., Jansson, John-Olov, Jula, Antti, Kahonen, Mika, Kathiresan, Sekar, Kee, Frank, Khaw, Kay-Tee, Kivimaki, Mika, Koenig, Wolfgang, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Laitinen, Jaana H., Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Lind, Lars, Lindstrom, Jaana, Liu, Jianjun, Liuzzi, Antonio, Lokki, Marja-Liisa, Lorentzon, Mattias, Madden, Pamela A., Magnusson, Patrik K., Manunta, Paolo, Marek, Diana, Maerz, Winfried, Leach, Irene Mateo, McKnight, Barbara, Medland, Sarah E., Mihailov, Evelin, Milani, Lili, Montgomery, Grant W., Mooser, Vincent, Muehleisen, Thomas W., Munroe, Patricia B., Musk, Arthur W., Narisu, Narisu, Navis, Gerjan, Nicholson, George, Nohr, Ellen A., Ong, Ken K., Oostra, Ben A., Palmer, Colin N. A., Palotie, Aarno, Peden, John F., Pedersen, Nancy, Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Prokopenko, Inga, Puetter, Carolin, Radhakrishnan, Aparna, Raitakari, Olli, Rendon, Augusto, Rivadeneira, Fernando, Rudan, Igor, Saaristo, Timo E., Sambrook, Jennifer G., Sanders, Alan R., Sanna, Serena, Saramies, Jouko, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Shin, So-Youn, Signorini, Stefano, Sinisalo, Juha, Skrobek, Boris, Soranzo, Nicole, Stancakova, Alena, Stark, Klaus, Stephens, Jonathan C., Stirrups, Kathleen, Stolk, Ronald P., Stumvoll, Michael, Swift, Amy J., Theodoraki, Eirini V., Thorand, Barbara, Tregouet, David-Alexandre, Tremoli, Elena, Van der Klauw, Melanie M., van Meurs, Joyce B. J., Vermeulen, Sita H., Viikari, Jorma, Virtamo, Jarmo, Vitart, Veronique, Waeber, Gerard, Wang, Zhaoming, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Winkelmann, Bernhard R., Witteman, Jacqueline C. M., Wolffenbuttel, Bruce H. R., Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Amouyel, Philippe, Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Cupples, L. Adrienne, Cusi, Daniele, Dedoussis, George V., Erdmann, Jeanette, Eriksson, Johan G., Franks, Paul W., Froguel, Philippe, Gieger, Christian, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hinney, Anke, Hofman, Albert, Hovingh, Kees G., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Joeckel, Karl-Heinz, Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Levinson, Douglas F., Martin, Nicholas G., Metspalu, Andres, Morris, Andrew D., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Ouwehand, Willem H., Palmer, Lyle J., Penninx, Brenda, Power, Chris, Province, Michael A., Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Ridker, Paul M., Ripatti, Samuli, Salomaa, Veikko, Samani, Nilesh J., Snieder, Harold, Sorensen, Thorkild I. A., Spector, Timothy D., Stefansson, Kari, Tonjes, Anke, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van der Harst, Pim, Vollenweider, Peter, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Wilson, James F., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunian, Talin, Heid, Iris M., Hunter, David, Kaplan, Robert C., Karpe, Fredrik, Moffatt, Miriam F., Mohlke, Karen L., O'Connell, Jeffrey R., Pawitan, Yudi, Schadt, Eric E., Schlessinger, David, Steinthorsdottir, Valgerdur, Strachan, David P., Thorsteinsdottir, Unnur, van Duijn, Cornelia M., Visscher, Peter M., Di Blasio, Anna Maria, Hirschhorn, Joel N., Lindgren, Cecilia M., Morris, Andrew P., Meyre, David, Scherag, Andr, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Loos, Ruth J. F., Ingelsson, Erik, Berndt, Sonja I., Gustafsson, Stefan, Maegi, Reedik, Ganna, Andrea, Wheeler, Eleanor, Feitosa, Mary F., Justice, Anne E., Monda, Keri L., Croteau-Chonka, Damien C., Day, Felix R., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gentilini, Davide, Jackson, Anne U., Luan, Jian'an, Randall, Joshua C., Vedantam, Sailaja, Willer, Cristen J., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Hu, Yi-Juan, Lee, Sang Hong, Liang, Liming, Lin, Dan-Yu, Min, Josine L., Neale, Benjamin M., Thorleifsson, Gudmar, Yang, Jian, Albrecht, Eva, Amin, Najaf, Bragg-Gresham, Jennifer L., Cadby, Gemma, den Heijer, Martin, Eklund, Niina, Fischer, Krista, Goel, Anuj, Hottenga, Jouke-Jan, Huffman, Jennifer E., Jarick, Ivonne, Johansson, Asa, Johnson, Toby, Kanoni, Stavroula, Kleber, Marcus E., Koenig, Inke R., Kristiansson, Kati, Kutalik, Zoltn, Lamina, Claudia, Lecoeur, Cecile, Li, Guo, Mangino, Massimo, McArdle, Wendy L., Medina-Gomez, Carolina, Mueller-Nurasyid, Martina, Ngwa, Julius S., Nolte, Ilja M., Paternoster, Lavinia, Pechlivanis, Sonali, Perola, Markus, Peters, Marjolein J., Preuss, Michael, Rose, Lynda M., Shi, Jianxin, Shungin, Dmitry, Smith, Albert Vernon, Strawbridge, Rona J., Surakka, Ida, Teumer, Alexander, Trip, Mieke D., Tyrer, Jonathan, Van Vliet-Ostaptchouk, Jana V., Vandenput, Liesbeth, Waite, Lindsay L., Zhao, Jing Hua, Absher, Devin, Asselbergs, Folkert W., Atalay, Mustafa, Attwood, Antony P., Balmforth, Anthony J., Basart, Hanneke, Beilby, John, Bonnycastle, Lori L., Brambilla, Paolo, Bruinenberg, Marcel, Campbell, Harry, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Connell, John M., Cookson, William O., de Faire, Ulf, de Vegt, Femmie, Dei, Mariano, Dimitriou, Maria, Edkins, Sarah, Estrada, Karol, Evans, David M., Farrall, Martin, Ferrario, Marco M., Ferrieres, Jean, Franke, Lude, Frau, Francesca, Gejman, Pablo V., Grallert, Harald, Groenberg, Henrik, Gudnason, Vilmundur, Hall, Alistair S., Hall, Per, Hartikainen, Anna-Liisa, Hayward, Caroline, Heard-Costa, Nancy L., Heath, Andrew C., Hebebrand, Johannes, Homuth, Georg, Hu, Frank B., Hunt, Sarah E., Hyppoenen, Elina, Iribarren, Carlos, Jacobs, Kevin B., Jansson, John-Olov, Jula, Antti, Kahonen, Mika, Kathiresan, Sekar, Kee, Frank, Khaw, Kay-Tee, Kivimaki, Mika, Koenig, Wolfgang, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Laitinen, Jaana H., Lakka, Timo A., Langenberg, Claudia, Launer, Lenore J., Lind, Lars, Lindstrom, Jaana, Liu, Jianjun, Liuzzi, Antonio, Lokki, Marja-Liisa, Lorentzon, Mattias, Madden, Pamela A., Magnusson, Patrik K., Manunta, Paolo, Marek, Diana, Maerz, Winfried, Leach, Irene Mateo, McKnight, Barbara, Medland, Sarah E., Mihailov, Evelin, Milani, Lili, Montgomery, Grant W., Mooser, Vincent, Muehleisen, Thomas W., Munroe, Patricia B., Musk, Arthur W., Narisu, Narisu, Navis, Gerjan, Nicholson, George, Nohr, Ellen A., Ong, Ken K., Oostra, Ben A., Palmer, Colin N. A., Palotie, Aarno, Peden, John F., Pedersen, Nancy, Peters, Annette, Polasek, Ozren, Pouta, Anneli, Pramstaller, Peter P., Prokopenko, Inga, Puetter, Carolin, Radhakrishnan, Aparna, Raitakari, Olli, Rendon, Augusto, Rivadeneira, Fernando, Rudan, Igor, Saaristo, Timo E., Sambrook, Jennifer G., Sanders, Alan R., Sanna, Serena, Saramies, Jouko, Schipf, Sabine, Schreiber, Stefan, Schunkert, Heribert, Shin, So-Youn, Signorini, Stefano, Sinisalo, Juha, Skrobek, Boris, Soranzo, Nicole, Stancakova, Alena, Stark, Klaus, Stephens, Jonathan C., Stirrups, Kathleen, Stolk, Ronald P., Stumvoll, Michael, Swift, Amy J., Theodoraki, Eirini V., Thorand, Barbara, Tregouet, David-Alexandre, Tremoli, Elena, Van der Klauw, Melanie M., van Meurs, Joyce B. J., Vermeulen, Sita H., Viikari, Jorma, Virtamo, Jarmo, Vitart, Veronique, Waeber, Gerard, Wang, Zhaoming, Widen, Elisabeth, Wild, Sarah H., Willemsen, Gonneke, Winkelmann, Bernhard R., Witteman, Jacqueline C. M., Wolffenbuttel, Bruce H. R., Wong, Andrew, Wright, Alan F., Zillikens, M. Carola, Amouyel, Philippe, Boehm, Bernhard O., Boerwinkle, Eric, Boomsma, Dorret I., Caulfield, Mark J., Chanock, Stephen J., Cupples, L. Adrienne, Cusi, Daniele, Dedoussis, George V., Erdmann, Jeanette, Eriksson, Johan G., Franks, Paul W., Froguel, Philippe, Gieger, Christian, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hengstenberg, Christian, Hicks, Andrew A., Hingorani, Aroon, Hinney, Anke, Hofman, Albert, Hovingh, Kees G., Hveem, Kristian, Illig, Thomas, Jarvelin, Marjo-Riitta, Joeckel, Karl-Heinz, Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Kuh, Diana, Laakso, Markku, Lehtimaki, Terho, Levinson, Douglas F., Martin, Nicholas G., Metspalu, Andres, Morris, Andrew D., Nieminen, Markku S., Njolstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J., Ouwehand, Willem H., Palmer, Lyle J., Penninx, Brenda, Power, Chris, Province, Michael A., Psaty, Bruce M., Qi, Lu, Rauramaa, Rainer, Ridker, Paul M., Ripatti, Samuli, Salomaa, Veikko, Samani, Nilesh J., Snieder, Harold, Sorensen, Thorkild I. A., Spector, Timothy D., Stefansson, Kari, Tonjes, Anke, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van der Harst, Pim, Vollenweider, Peter, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Wilson, James F., Abecasis, Goncalo R., Assimes, Themistocles L., Barroso, Ines, Boehnke, Michael, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Frayling, Timothy, Groop, Leif C., Haritunian, Talin, Heid, Iris M., Hunter, David, Kaplan, Robert C., Karpe, Fredrik, Moffatt, Miriam F., Mohlke, Karen L., O'Connell, Jeffrey R., Pawitan, Yudi, Schadt, Eric E., Schlessinger, David, Steinthorsdottir, Valgerdur, Strachan, David P., Thorsteinsdottir, Unnur, van Duijn, Cornelia M., Visscher, Peter M., Di Blasio, Anna Maria, Hirschhorn, Joel N., Lindgren, Cecilia M., Morris, Andrew P., Meyre, David, Scherag, Andr, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Loos, Ruth J. F., and Ingelsson, Erik
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
Published: 2013
Full Text: View/download PDF

25. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Author: Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, Heid, Iris M, Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, and Heid, Iris M
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Published: 2013
Full Text: View/download PDF

26. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Author: Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, Heid, Iris M, Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, and Heid, Iris M
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Published: 2013
Full Text: View/download PDF

27. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Author: Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, Heid, Iris M, Randall, Joshua C, Winkler, Thomas W, Kutalik, Zoltán, Berndt, Sonja I, Jackson, Anne U, Monda, Keri L, Kilpeläinen, Tuomas O, Esko, Tõnu, Mägi, Reedik, Li, Shengxu, Workalemahu, Tsegaselassie, Feitosa, Mary F, Croteau-Chonka, Damien C, Day, Felix R, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Locke, Adam E, Mathieson, Iain, Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R, Liang, Liming, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Dermitzakis, Emmanouil T, Dimas, Antigone S, Karpe, Fredrik, Min, Josine L, Nicholson, George, Clegg, Deborah J, Person, Thomas, Krohn, Jon P, Bauer, Sabrina, Buechler, Christa, Eisinger, Kristina, Bonnefond, Amélie, Froguel, Philippe, Hottenga, Jouke-Jan, Prokopenko, Inga, Waite, Lindsay L, Harris, Tamara B, Smith, Albert Vernon, Shuldiner, Alan R, McArdle, Wendy L, Caulfield, Mark J, Munroe, Patricia B, Grönberg, Henrik, Chen, Yii-Der Ida, Li, Guo, Beckmann, Jacques S, Johnson, Toby, Thorsteinsdottir, Unnur, Teder-Laving, Maris, Khaw, Kay-Tee, Wareham, Nicholas J, Zhao, Jing Hua, Amin, Najaf, Oostra, Ben A, Kraja, Aldi T, Province, Michael A, Cupples, L Adrienne, Heard-Costa, Nancy L, Kaprio, Jaakko, Ripatti, Samuli, Surakka, Ida, Collins, Francis S, Saramies, Jouko, Tuomilehto, Jaakko, Jula, Antti, Salomaa, Veikko, Erdmann, Jeanette, Hengstenberg, Christian, Loley, Christina, Schunkert, Heribert, Lamina, Claudia, Wichmann, H Erich, Albrecht, Eva, Gieger, Christian, Hicks, Andrew A, Johansson, Asa, Pramstaller, Peter P, Kathiresan, Sekar, Speliotes, Elizabeth K, Penninx, Brenda, Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Gyllensten, Ulf, Boomsma, Dorret I, Campbell, Harry, Wilson, James F, Chanock, Stephen J, Farrall, Martin, Goel, Anuj, Medina-Gomez, Carolina, Rivadeneira, Fernando, Estrada, Karol, Uitterlinden, André G, Hofman, Albert, Zillikens, M Carola, den Heijer, Martin, Kiemeney, Lambertus A, Maschio, Andrea, Hall, Per, Tyrer, Jonathan, Teumer, Alexander, Völzke, Henry, Kovacs, Peter, Tönjes, Anke, Mangino, Massimo, Spector, Tim D, Hayward, Caroline, Rudan, Igor, Hall, Alistair S, Samani, Nilesh J, Attwood, Antony Paul, Sambrook, Jennifer G, Hung, Joseph, Palmer, Lyle J, Lokki, Marja-Liisa, Sinisalo, Juha, Boucher, Gabrielle, Huikuri, Heikki, Lorentzon, Mattias, Ohlsson, Claes, Eklund, Niina, Eriksson, Johan G, Barlassina, Cristina, Rivolta, Carlo, Nolte, Ilja M, Snieder, Harold, Van der Klauw, Melanie M, Van Vliet-Ostaptchouk, Jana V, Gejman, Pablo V, Shi, Jianxin, Jacobs, Kevin B, Wang, Zhaoming, Bakker, Stephan J L, Mateo Leach, Irene, Navis, Gerjan, van der Harst, Pim, Martin, Nicholas G, Medland, Sarah E, Montgomery, Grant W, Yang, Jian, Chasman, Daniel I, Ridker, Paul M, Rose, Lynda M, Lehtimäki, Terho, Raitakari, Olli, Absher, Devin, Iribarren, Carlos, Basart, Hanneke, Hovingh, Kees G, Hyppönen, Elina, Power, Chris, Anderson, Denise, Beilby, John P, Hui, Jennie, Jolley, Jennifer, Sager, Hendrik, Bornstein, Stefan R, Schwarz, Peter E H, Kristiansson, Kati, Perola, Markus, Lindström, Jaana, Swift, Amy J, Uusitupa, Matti, Atalay, Mustafa, Lakka, Timo A, Rauramaa, Rainer, Bolton, Jennifer L, Fowkes, Gerry, Fraser, Ross M, Price, Jackie F, Fischer, Krista, Krjutå Kov, Kaarel, Metspalu, Andres, Mihailov, Evelin, Langenberg, Claudia, Luan, Jian'an, Ong, Ken K, Chines, Peter S, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Edkins, Sarah, Franks, Paul W, Hallmans, Göran, Shungin, Dmitry, Morris, Andrew David, Palmer, Colin N A, Erbel, Raimund, Moebus, Susanne, Nöthen, Markus M, Pechlivanis, Sonali, Hveem, Kristian, Narisu, Narisu, Hamsten, Anders, Humphries, Steve E, Strawbridge, Rona J, Tremoli, Elena, Grallert, Harald, Thorand, Barbara, Illig, Thomas, Koenig, Wolfgang, Müller-Nurasyid, Martina, Peters, Annette, Boehm, Bernhard O, Kleber, Marcus E, März, Winfried, Winkelmann, Bernhard R, Kuusisto, Johanna, Laakso, Markku, Arveiler, Dominique, Cesana, Giancarlo, Kuulasmaa, Kari, Virtamo, Jarmo, Yarnell, John W G, Kuh, Diana, Wong, Andrew, Lind, Lars, de Faire, Ulf, Gigante, Bruna, Magnusson, Patrik K E, Pedersen, Nancy L, Dedoussis, George, Dimitriou, Maria, Kolovou, Genovefa, Kanoni, Stavroula, Stirrups, Kathleen, Bonnycastle, Lori L, Njølstad, Inger, Wilsgaard, Tom, Ganna, Andrea, Rehnberg, Emil, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Assimes, Themistocles L, Barroso, Inês, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Fox, Caroline S, Frayling, Timothy, Groop, Leif C, Haritunians, Talin, Hunter, David, Ingelsson, Erik, Kaplan, Robert, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Abecasis, Gonçalo R, McCarthy, Mark I, Hirschhorn, Joel N, Qi, Lu, Loos, Ruth J F, Lindgren, Cecilia M, North, Kari E, and Heid, Iris M
Abstract: Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
Published: 2013
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27 results on '"Winkler, Thomas W"'

1. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

2. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

3. Rare and low-frequency coding variants alter human adult height

4. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

5. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

6. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

7. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

8. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

9. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

10. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

11. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

12. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

13. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

14. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

15. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

16. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

17. Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

18. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

19. Genetic studies of body mass index yield new insights for obesity biology

20. New genetic loci link adipose and insulin biology to body fat distribution

21. Defining the role of common variation in the genomic and biological architecture of adult human height

22. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

23. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

24. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

25. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

26. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

27. Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

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27 results on '"Winkler, Thomas W"'

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