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25 results on '"Perry, John"'

1. Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation

Author

Radford, Elizabeth J., Tan, Hong-Kee, Andersson, Malin H. L., Stephenson, James D., Gardner, Eugene J., Ironfield, Holly, Waters, Andrew J., Gitterman, Daniel, Lindsay, Sarah, Abascal, Federico, Martincorena, Iñigo, Kolesnik-Taylor, Anna, Ng-Cordell, Elise, Firth, Helen V., Baker, Kate, Perry, John R. B., Adams, David J., Gerety, Sebastian S., and Hurles, Matthew E.

Published
2023
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4. GWAS of epigenetic aging rates in blood reveals a critical role for TERT.

Author

Lu, Ake T, Xue, Luting, Salfati, Elias L, Chen, Brian H, Ferrucci, Luigi, Levy, Daniel, Joehanes, Roby, Murabito, Joanne M, Kiel, Douglas P, Tsai, Pei-Chien, Yet, Idil, Bell, Jordana T, Mangino, Massimo, Tanaka, Toshiko, McRae, Allan F, Marioni, Riccardo E, Visscher, Peter M, Wray, Naomi R, Deary, Ian J, Levine, Morgan E, Quach, Austin, Assimes, Themistocles, Tsao, Philip S, Absher, Devin, Stewart, James D, Li, Yun, Reiner, Alex P, Hou, Lifang, Baccarelli, Andrea A, Whitsel, Eric A, Aviv, Abraham, Cardona, Alexia, Day, Felix R, Wareham, Nicholas J, Perry, John RB, Ong, Ken K, Raj, Kenneth, Lunetta, Kathryn L, and Horvath, Steve

Subjects
Leukocytes, Cells, Cultured, Telomere, Fibroblasts, Humans, Telomerase, DNA Methylation, Epigenesis, Genetic, CpG Islands, Aging, Menopause, Menarche, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Genome-Wide Association Study, Young Adult, Mendelian Randomization Analysis, Cells, Cultured, Epigenesis, Genetic, and over
Abstract

DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P

Published
2018

5. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.

Author

Willems, Sara M, Wright, Daniel J, Day, Felix R, Trajanoska, Katerina, Joshi, Peter K, Morris, John A, Matteini, Amy M, Garton, Fleur C, Grarup, Niels, Oskolkov, Nikolay, Thalamuthu, Anbupalam, Mangino, Massimo, Liu, Jun, Demirkan, Ayse, Lek, Monkol, Xu, Liwen, Wang, Guan, Oldmeadow, Christopher, Gaulton, Kyle J, Lotta, Luca A, Miyamoto-Mikami, Eri, Rivas, Manuel A, White, Tom, Loh, Po-Ru, Aadahl, Mette, Amin, Najaf, Attia, John R, Austin, Krista, Benyamin, Beben, Brage, Søren, Cheng, Yu-Ching, Cięszczyk, Paweł, Derave, Wim, Eriksson, Karl-Fredrik, Eynon, Nir, Linneberg, Allan, Lucia, Alejandro, Massidda, Myosotis, Mitchell, Braxton D, Miyachi, Motohiko, Murakami, Haruka, Padmanabhan, Sandosh, Pandey, Ashutosh, Papadimitriou, Ioannis, Rajpal, Deepak K, Sale, Craig, Schnurr, Theresia M, Sessa, Francesco, Shrine, Nick, Tobin, Martin D, Varley, Ian, Wain, Louise V, Wray, Naomi R, Lindgren, Cecilia M, MacArthur, Daniel G, Waterworth, Dawn M, McCarthy, Mark I, Pedersen, Oluf, Khaw, Kay-Tee, Kiel, Douglas P, GEFOS Any-Type of Fracture Consortium, Pitsiladis, Yannis, Fuku, Noriyuki, Franks, Paul W, North, Kathryn N, van Duijn, Cornelia M, Mather, Karen A, Hansen, Torben, Hansson, Ola, Spector, Tim, Murabito, Joanne M, Richards, J Brent, Rivadeneira, Fernando, Langenberg, Claudia, Perry, John RB, Wareham, Nick J, and Scott, Robert A

Subjects
GEFOS Any-Type of Fracture Consortium, Hand, Humans, Actins, Transforming Growth Factor alpha, Membrane Proteins, Neoplasm Proteins, Nuclear Proteins, Repressor Proteins, Hand Strength, Cohort Studies, Genetics, Population, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Genetic Loci, United Kingdom, Prevention, Genetics, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Musculoskeletal
Abstract

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P

Published
2017

6. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author

Lagou, Vasiliki, Mägi, Reedik, Hottenga, Jouke- Jan, Grallert, Harald, Perry, John R. B., Bouatia-Naji, Nabila, Marullo, Letizia, Rybin, Denis, Jansen, Rick, Min, Josine L., Dimas, Antigone S., Ulrich, Anna, Zudina, Liudmila, Gådin, Jesper R., Jiang, Longda, Faggian, Alessia, Bonnefond, Amélie, Fadista, Joao, Stathopoulou, Maria G., Isaacs, Aaron, Willems, Sara M., Navarro, Pau, Tanaka, Toshiko, Jackson, Anne U., Montasser, May E., O’Connell, Jeff R., Bielak, Lawrence F., Webster, Rebecca J., Saxena, Richa, Stafford, Jeanette M., Pourcain, Beate St, Timpson, Nicholas J., Salo, Perttu, Shin, So-Youn, Amin, Najaf, Smith, Albert V., Li, Guo, Verweij, Niek, Goel, Anuj, Ford, Ian, Johnson, Paul C. D., Johnson, Toby, Kapur, Karen, Thorleifsson, Gudmar, Strawbridge, Rona J., Rasmussen-Torvik, Laura J., Esko, Tõnu, Mihailov, Evelin, Fall, Tove, Fraser, Ross M., Mahajan, Anubha, Kanoni, Stavroula, Giedraitis, Vilmantas, Kleber, Marcus E., Silbernagel, Günther, Meyer, Julia, Müller-Nurasyid, Martina, Ganna, Andrea, Sarin, Antti-Pekka, Yengo, Loic, Shungin, Dmitry, Luan, Jian’an, Horikoshi, Momoko, An, Ping, Sanna, Serena, Boettcher, Yvonne, Rayner, N. William, Nolte, Ilja M., Zemunik, Tatijana, Iperen, Erik van, Kovacs, Peter, Hastie, Nicholas D., Wild, Sarah H., McLachlan, Stela, Campbell, Susan, Polasek, Ozren, Carlson, Olga, Egan, Josephine, Kiess, Wieland, Willemsen, Gonneke, Kuusisto, Johanna, Laakso, Markku, Dimitriou, Maria, Hicks, Andrew A., Rauramaa, Rainer, Bandinelli, Stefania, Thorand, Barbara, Liu, Yongmei, Miljkovic, Iva, Lind, Lars, Doney, Alex, Perola, Markus, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Bennett, Amanda J., Groves, Christopher J., Herder, Christian, Koistinen, Heikki A., Kinnunen, Leena, Faire, Ulf de, Bakker, Stephan J. L., Uusitupa, Matti, Palmer, Colin N. A., Jukema, J. Wouter, Sattar, Naveed, Pouta, Anneli, Snieder, Harold, Boerwinkle, Eric, Pankow, James S., Magnusson, Patrik K., Krus, Ulrika, Scapoli, Chiara, de Geus, Eco J. C. N., Blüher, Matthias, Wolffenbuttel, Bruce H. R., Province, Michael A., Abecasis, Goncalo R., Meigs, James B., Hovingh, G. Kees, Lindström, Jaana, Wilson, James F., Wright, Alan F., Dedoussis, George V., Bornstein, Stefan R., Schwarz, Peter E. H., Tönjes, Anke, Winkelmann, Bernhard R., Boehm, Bernhard O., März, Winfried, Metspalu, Andres, Price, Jackie F., Deloukas, Panos, Körner, Antje, Lakka, Timo A., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Bergman, Richard N., Tuomilehto, Jaakko, Wareham, Nicholas J., Langenberg, Claudia, Männistö, Satu, Franks, Paul W., Hayward, Caroline, Vitart, Veronique, Kaprio, Jaakko, Visvikis-Siest, Sophie, Balkau, Beverley, Altshuler, David, Rudan, Igor, Stumvoll, Michael, Campbell, Harry, van Duijn, Cornelia M., Gieger, Christian, Illig, Thomas, Ferrucci, Luigi, Pedersen, Nancy L., Pramstaller, Peter P., Boehnke, Michael, Frayling, Timothy M., Shuldiner, Alan R., Peyser, Patricia A., Kardia, Sharon L. R., Palmer, Lyle J., Penninx, Brenda W., Meneton, Pierre, Harris, Tamara B., Navis, Gerjan, Harst, Pim van der, Smith, George Davey, Forouhi, Nita G., Loos, Ruth J. F., Salomaa, Veikko, Soranzo, Nicole, Boomsma, Dorret I., Groop, Leif, Tuomi, Tiinamaija, Hofman, Albert, Munroe, Patricia B., Gudnason, Vilmundur, Siscovick, David S., Watkins, Hugh, Lecoeur, Cecile, Vollenweider, Peter, Franco-Cereceda, Anders, Eriksson, Per, Jarvelin, Marjo-Riitta, Stefansson, Kari, Hamsten, Anders, Nicholson, George, Karpe, Fredrik, Dermitzakis, Emmanouil T., Lindgren, Cecilia M., McCarthy, Mark I., Froguel, Philippe, Kaakinen, Marika A., Lyssenko, Valeriya, Watanabe, Richard M., Ingelsson, Erik, Florez, Jose C., Dupuis, Josée, Barroso, Inês, Morris, Andrew P., and Prokopenko, Inga

Published
2021
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7. Associations of autozygosity with a broad range of human phenotypes

Author

Clark, David W, Okada, Yukinori, Moore, Kristjan H S, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona L K, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, de Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, van der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, van der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, de Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, Chen, Guanjie, Chen, Yii-Der I, Chen, Zhengming, Chiu, Yen-Feng, Cocca, Massimiliano, Collins, Francis S, Concas, Maria Pina, Corley, Janie, Cugliari, Giovanni, van Dam, Rob M, Damulina, Anna, Daneshpour, Maryam S, Day, Felix R, Delgado, Graciela E, Dhana, Klodian, Doney, Alexander S F, Dörr, Marcus, Doumatey, Ayo P, Dzimiri, Nduna, Ebenesersdóttir, S Sunna, Elliott, Joshua, Elliott, Paul, Ewert, Ralf, Felix, Janine F, Fischer, Krista, Freedman, Barry I, Girotto, Giorgia, Goel, Anuj, Gögele, Martin, Goodarzi, Mark O, Graff, Mariaelisa, Granot-Hershkovitz, Einat, Grodstein, Francine, Guarrera, Simonetta, Gudbjartsson, Daniel F, Guity, Kamran, Gunnarsson, Bjarni, Guo, Yu, Hagenaars, Saskia P, Haiman, Christopher A, Halevy, Avner, Harris, Tamara B, Hedayati, Mehdi, van Heel, David A, Hirata, Makoto, Höfer, Imo, Hsiung, Chao Agnes, Huang, Jinyan, Hung, Yi-Jen, Ikram, M Arfan, Jagadeesan, Anuradha, Jousilahti, Pekka, Kamatani, Yoichiro, Kanai, Masahiro, Kerrison, Nicola D, Kessler, Thorsten, Khaw, Kay-Tee, Khor, Chiea Chuen, de Kleijn, Dominique P V, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter, Krämer, Bernhard K, Kutalik, Zoltán, Kuusisto, Johanna, Langenberg, Claudia, Launer, Lenore J, Lawlor, Deborah A, Lee, I-Te, Lee, Wen-Jane, Lerch, Markus M, Li, Liming, Liu, Jianjun, Loh, Marie, London, Stephanie J, Loomis, Stephanie, Lu, Yingchang, Luan, Jian’an, Mägi, Reedik, Manichaikul, Ani W, Manunta, Paolo, Másson, Gísli, Matoba, Nana, Mei, Xue W, Meisinger, Christa, Meitinger, Thomas, Mezzavilla, Massimo, Milani, Lili, Millwood, Iona Y, Momozawa, Yukihide, Moore, Amy, Morange, Pierre-Emmanuel, Moreno-Macías, Hortensia, Mori, Trevor A, Morrison, Alanna C, Muka, Taulant, Murakami, Yoshinori, Murray, Alison D, de Mutsert, Renée, Mychaleckyj, Josyf C, Nalls, Mike A, Nauck, Matthias, Neville, Matt J, Nolte, Ilja M, Ong, Ken K, Orozco, Lorena, Padmanabhan, Sandosh, Pálsson, Gunnar, Pankow, James S, Pattaro, Cristian, Pattie, Alison, Polasek, Ozren, Poulter, Neil, Pramstaller, Peter P, Quintana-Murci, Lluis, Räikkönen, Katri, Ralhan, Sarju, Rao, Dabeeru C, van Rheenen, Wouter, Rich, Stephen S, Ridker, Paul M, Rietveld, Cornelius A, Robino, Antonietta, van Rooij, Frank J A, Ruggiero, Daniela, Saba, Yasaman, Sabanayagam, Charumathi, Sabater-Lleal, Maria, Sala, Cinzia Felicita, Salomaa, Veikko, Sandow, Kevin, Schmidt, Helena, Scott, Laura J, Scott, William R, Sedaghati-Khayat, Bahareh, Sennblad, Bengt, van Setten, Jessica, Sever, Peter J, Sheu, Wayne H-H, Shi, Yuan, Shrestha, Smeeta, Shukla, Sharvari Rahul, Sigurdsson, Jon K, Sikka, Timo Tonis, Singh, Jai Rup, Smith, Blair H, Stančáková, Alena, Stanton, Alice, Starr, John M, Stefansdottir, Lilja, Straker, Leon, Sulem, Patrick, Sveinbjornsson, Gardar, Swertz, Morris A, Taylor, Adele M, Taylor, Kent D, Terzikhan, Natalie, Tham, Yih-Chung, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tillander, Annika, Tracy, Russell P, Tusié-Luna, Teresa, Tzoulaki, Ioanna, Vaccargiu, Simona, Vangipurapu, Jagadish, Veldink, Jan H, Vitart, Veronique, Völker, Uwe, Vuoksimaa, Eero, Wakil, Salma M, Waldenberger, Melanie, Wander, Gurpreet S, Wang, Ya Xing, Wareham, Nicholas J, Wild, Sarah, Yajnik, Chittaranjan S, Yuan, Jian-Min, Zeng, Lingyao, Zhang, Liang, Zhou, Jie, Amin, Najaf, Asselbergs, Folkert W, Bakker, Stephan J L, Becker, Diane M, Lehne, Benjamin, Bennett, David A, van den Berg, Leonard H, Berndt, Sonja I, Bharadwaj, Dwaipayan, Bielak, Lawrence F, Bochud, Murielle, Boehnke, Mike, Bouchard, Claude, Bradfield, Jonathan P, Brody, Jennifer A, Campbell, Archie, Carmi, Shai, Caulfield, Mark J, Cesarini, David, Chambers, John C, Chandak, Giriraj Ratan, Cheng, Ching-Yu, Ciullo, Marina, Cornelis, Marilyn, Cusi, Daniele, Smith, George Davey, Deary, Ian J, Dorajoo, Rajkumar, van Duijn, Cornelia M, Ellinghaus, David, Erdmann, Jeanette, Eriksson, Johan G, Evangelou, Evangelos, Evans, Michele K, Faul, Jessica D, Feenstra, Bjarke, Feitosa, Mary, Foisy, Sylvain, Franke, Andre, Friedlander, Yechiel, Gasparini, Paolo, Gieger, Christian, Gonzalez, Clicerio, Goyette, Philippe, Grant, Struan F A, Griffiths, Lyn R, Groop, Leif, Gudnason, Vilmundur, Gyllensten, Ulf, Hakonarson, Hakon, Hamsten, Anders, van der Harst, Pim, Heng, Chew-Kiat, Hicks, Andrew A, Hochner, Hagit, Huikuri, Heikki, Hunt, Steven C, Jaddoe, Vincent W V, De Jager, Philip L, Johannesson, Magnus, Johansson, Åsa, Jonas, Jost B, Jukema, J Wouter, Junttila, Juhani, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kumari, Meena, Laakso, Markku, van der Laan, Sander W, Lahti, Jari, Laudes, Matthias, Lea, Rodney A, Lieb, Wolfgang, Lumley, Thomas, Martin, Nicholas G, März, Winfried, Matullo, Giuseppe, McCarthy, Mark I, Medland, Sarah E, Merriman, Tony R, Metspalu, Andres, Meyer, Brian F, Mohlke, Karen L, Montgomery, Grant W, Mook-Kanamori, Dennis, Munroe, Patricia B, North, Kari E, Nyholt, Dale R, O’connell, Jeffery R, Ober, Carole, Oldehinkel, Albertine J, Palmas, Walter, Palmer, Colin, Pasterkamp, Gerard G, Patin, Etienne, Pennell, Craig E, Perusse, Louis, Peyser, Patricia A, Pirastu, Mario, Polderman, Tinca J. C., Porteous, David J, Posthuma, Danielle, Psaty, Bruce M, Rioux, John D, Rivadeneira, Fernando, Rotimi, Charles, Rotter, Jerome I, Rudan, Igor, Den Ruijter, Hester M, Sanghera, Dharambir K, Sattar, Naveed, Schmidt, Reinhold, Schulze, Matthias B, Schunkert, Heribert, Scott, Robert A, Shuldiner, Alan R, Sim, Xueling, Small, Neil, Smith, Jennifer A, Sotoodehnia, Nona, Tai, E-Shyong, Teumer, Alexander, Timpson, Nicholas J, Toniolo, Daniela, Tregouet, David-Alexandre, Tuomi, Tiinamaija, Vollenweider, Peter, Wang, Carol A, Weir, David R, Whitfield, John B, Wijmenga, Cisca, Wong, Tien-Yin, Wright, John, Yang, Jingyun, Yu, Lei, Zemel, Babette S, Zonderman, Alan B, Perola, Markus, Magnusson, Patrik K. E., Uitterlinden, André G, Kooner, Jaspal S, Chasman, Daniel I, Loos, Ruth J. F., Franceschini, Nora, Franke, Lude, Haley, Chris S, Hayward, Caroline, Walters, Robin G, Perry, John R. B., Esko, Tōnu, Helgason, Agnar, Stefansson, Kari, Joshi, Peter K, Kubo, Michiaki, and Wilson, James F

Published
2019
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9. GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health

Author

Zhao, Yajie, primary, Stankovic, Stasa, additional, Koprulu, Mine, additional, Wheeler, Eleanor, additional, Day, Felix R., additional, Lango Allen, Hana, additional, Kerrison, Nicola D., additional, Pietzner, Maik, additional, Loh, Po-Ru, additional, Wareham, Nicholas J., additional, Langenberg, Claudia, additional, Ong, Ken K., additional, and Perry, John R. B., additional

Published
2021
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10. Correction: Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author

Lunetta, Kathryn L., Day, Felix R., Sulem, Patrick, Ruth, Katherine S., Tung, Joyce Y., Hinds, David A., Esko, Tõnu, Elks, Cathy E., Altmaier, Elisabeth, He, Chunyan, Huffman, Jennifer E., Mihailov, Evelin, Porcu, Eleonora, Robino, Antonietta, Rose, Lynda M., Schick, Ursula M., Stolk, Lisette, Teumer, Alexander, Thompson, Deborah J., Traglia, Michela, Wang, Carol A., Yerges-Armstrong, Laura M., Antoniou, Antonis C., Barbieri, Caterina, Coviello, Andrea D., Cucca, Francesco, Demerath, Ellen W., Dunning, Alison M., Gandin, Ilaria, Grove, Megan L., Gudbjartsson, Daniel F., Hocking, Lynne J., Hofman, Albert, Huang, Jinyan, Jackson, Rebecca D., Karasik, David, Kriebel, Jennifer, Lange, Ethan M., Lange, Leslie A., Langenberg, Claudia, Li, Xin, Luan, Jian'an, Mägi, Reedik, Morrison, Alanna C., Padmanabhan, Sandosh, Pirie, Ailith, Polasek, Ozren, Porteous, David, Reiner, Alex P., Rivadeneira, Fernando, Rudan, Igor, Sala, Cinzia F., Schlessinger, David, Scott, Robert A., Stöckl, Doris, Visser, Jenny A., Völker, Uwe, Vozzi, Diego, Wilson, James G., Zygmunt, Marek, Boerwinkle, Eric, Buring, Julie E., Crisponi, Laura, Easton, Douglas F., Hayward, Caroline, Hu, Frank B., Liu, Simin, Metspalu, Andres, Pennell, Craig E., Ridker, Paul M., Strauch, Konstantin, Streeten, Elizabeth A., Toniolo, Daniela, Uitterlinden, André G., Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Wellons, Melissa, Franceschini, Nora, Chasman, Daniel I., Thorsteinsdottir, Unnur, Murray, Anna, Stefansson, Kari, Murabito, Joanne M., Ong, Ken K., and Perry, John R. B.

Published
2015
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11. Identification of nine new susceptibility loci for endometrial cancer

Author

O’Mara, Tracy A., primary, Glubb, Dylan M., additional, Amant, Frederic, additional, Annibali, Daniela, additional, Ashton, Katie, additional, Attia, John, additional, Auer, Paul L., additional, Beckmann, Matthias W., additional, Black, Amanda, additional, Bolla, Manjeet K., additional, Brauch, Hiltrud, additional, Brenner, Hermann, additional, Brinton, Louise, additional, Buchanan, Daniel D., additional, Burwinkel, Barbara, additional, Chang-Claude, Jenny, additional, Chanock, Stephen J., additional, Chen, Chu, additional, Chen, Maxine M., additional, Cheng, Timothy H. T., additional, Clarke, Christine L., additional, Clendenning, Mark, additional, Cook, Linda S., additional, Couch, Fergus J., additional, Cox, Angela, additional, Crous-Bous, Marta, additional, Czene, Kamila, additional, Day, Felix, additional, Dennis, Joe, additional, Depreeuw, Jeroen, additional, Doherty, Jennifer Anne, additional, Dörk, Thilo, additional, Dowdy, Sean C., additional, Dürst, Matthias, additional, Ekici, Arif B., additional, Fasching, Peter A., additional, Fridley, Brooke L., additional, Friedenreich, Christine M., additional, Fritschi, Lin, additional, Fung, Jenny, additional, García-Closas, Montserrat, additional, Gaudet, Mia M., additional, Giles, Graham G., additional, Goode, Ellen L., additional, Gorman, Maggie, additional, Haiman, Christopher A., additional, Hall, Per, additional, Hankison, Susan E., additional, Healey, Catherine S., additional, Hein, Alexander, additional, Hillemanns, Peter, additional, Hodgson, Shirley, additional, Hoivik, Erling A., additional, Holliday, Elizabeth G., additional, Hopper, John L., additional, Hunter, David J., additional, Jones, Angela, additional, Krakstad, Camilla, additional, Kristensen, Vessela N., additional, Lambrechts, Diether, additional, Marchand, Loic Le, additional, Liang, Xiaolin, additional, Lindblom, Annika, additional, Lissowska, Jolanta, additional, Long, Jirong, additional, Lu, Lingeng, additional, Magliocco, Anthony M., additional, Martin, Lynn, additional, McEvoy, Mark, additional, Meindl, Alfons, additional, Michailidou, Kyriaki, additional, Milne, Roger L., additional, Mints, Miriam, additional, Montgomery, Grant W., additional, Nassir, Rami, additional, Olsson, Håkan, additional, Orlow, Irene, additional, Otton, Geoffrey, additional, Palles, Claire, additional, Perry, John R. B., additional, Peto, Julian, additional, Pooler, Loreall, additional, Prescott, Jennifer, additional, Proietto, Tony, additional, Rebbeck, Timothy R., additional, Risch, Harvey A., additional, Rogers, Peter A. W., additional, Rübner, Matthias, additional, Runnebaum, Ingo, additional, Sacerdote, Carlotta, additional, Sarto, Gloria E., additional, Schumacher, Fredrick, additional, Scott, Rodney J., additional, Setiawan, V. Wendy, additional, Shah, Mitul, additional, Sheng, Xin, additional, Shu, Xiao-Ou, additional, Southey, Melissa C., additional, Swerdlow, Anthony J., additional, Tham, Emma, additional, Trovik, Jone, additional, Turman, Constance, additional, Tyrer, Jonathan P., additional, Vachon, Celine, additional, VanDen Berg, David, additional, Vanderstichele, Adriaan, additional, Wang, Zhaoming, additional, Webb, Penelope M., additional, Wentzensen, Nicolas, additional, Werner, Henrica M. J., additional, Winham, Stacey J., additional, Wolk, Alicja, additional, Xia, Lucy, additional, Xiang, Yong-Bing, additional, Yang, Hannah P., additional, Yu, Herbert, additional, Zheng, Wei, additional, Pharoah, Paul D. P., additional, Dunning, Alison M., additional, Kraft, Peter, additional, De Vivo, Immaculata, additional, Tomlinson, Ian, additional, Easton, Douglas F., additional, Spurdle, Amanda B., additional, and Thompson, Deborah J., additional

Published
2018
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13. Elucidating the genetic architecture of reproductive ageing in the Japanese population

Author

Horikoshi, Momoko, primary, Day, Felix R., additional, Akiyama, Masato, additional, Hirata, Makoto, additional, Kamatani, Yoichiro, additional, Matsuda, Koichi, additional, Ishigaki, Kazuyoshi, additional, Kanai, Masahiro, additional, Wright, Hollis, additional, Toro, Carlos A., additional, Ojeda, Sergio R., additional, Lomniczi, Alejandro, additional, Kubo, Michiaki, additional, Ong, Ken K., additional, and Perry, John. R. B., additional

Published
2018
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14. Erratum: A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

Author

Timpson, Nicholas J., Walter, Klaudia, Min, Josine L., Tachmazidou, Ioanna, Malerba, Giovanni, Shin, So-Youn, Chen, Lu, Futema, Marta, Southam, Lorraine, Iotchkova, Valentina, Cocca, Massimiliano, Huang, Jie, Memari, Yasin, McCarthy, Shane, Danecek, Petr, Muddyman, Dawn, Mangino, Massimo, Menni, Cristina, Perry, John R. B., Ring, Susan M., Gaye, Amadou, Dedoussis, George, Farmaki, Aliki-Eleni, Burton, Paul, Talmud, Philippa J., Gambaro, Giovanni, Spector, Tim D., Smith, George Davey, Durbin, Richard, Richards, J. Brent, Humphries, Steve E., Zeggini, Eleftheria, and Soranzo, Nicole

Subjects
Male, Apolipoprotein C-III, Multidisciplinary, Polymorphism, Genetic, Twins, General Physics and Astronomy, General Chemistry, Lipoproteins, VLDL, Middle Aged, General Biochemistry, Genetics and Molecular Biology, White People, Alternative Splicing, Gene Frequency, Humans, Female, Erratum, Child, Lipoproteins, HDL, Alleles, Triglycerides
Abstract

The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 × 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.

Published
2015

15. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Lu, Yingchang, primary, Day, Felix R., additional, Gustafsson, Stefan, additional, Buchkovich, Martin L., additional, Na, Jianbo, additional, Bataille, Veronique, additional, Cousminer, Diana L., additional, Dastani, Zari, additional, Drong, Alexander W., additional, Esko, Tõnu, additional, Evans, David M., additional, Falchi, Mario, additional, Feitosa, Mary F., additional, Ferreira, Teresa, additional, Hedman, Åsa K., additional, Haring, Robin, additional, Hysi, Pirro G., additional, Iles, Mark M., additional, Justice, Anne E., additional, Kanoni, Stavroula, additional, Lagou, Vasiliki, additional, Li, Rui, additional, Li, Xin, additional, Locke, Adam, additional, Lu, Chen, additional, Mägi, Reedik, additional, Perry, John R. B., additional, Pers, Tune H., additional, Qi, Qibin, additional, Sanna, Marianna, additional, Schmidt, Ellen M., additional, Scott, William R., additional, Shungin, Dmitry, additional, Teumer, Alexander, additional, Vinkhuyzen, Anna A. E., additional, Walker, Ryan W., additional, Westra, Harm-Jan, additional, Zhang, Mingfeng, additional, Zhang, Weihua, additional, Zhao, Jing Hua, additional, Zhu, Zhihong, additional, Afzal, Uzma, additional, Ahluwalia, Tarunveer Singh, additional, Bakker, Stephan J. L., additional, Bellis, Claire, additional, Bonnefond, Amélie, additional, Borodulin, Katja, additional, Buchman, Aron S., additional, Cederholm, Tommy, additional, Choh, Audrey C., additional, Choi, Hyung Jin, additional, Curran, Joanne E., additional, de Groot, Lisette C. P. G. M., additional, De Jager, Philip L., additional, Dhonukshe-Rutten, Rosalie A. M., additional, Enneman, Anke W., additional, Eury, Elodie, additional, Evans, Daniel S., additional, Forsen, Tom, additional, Friedrich, Nele, additional, Fumeron, Frédéric, additional, Garcia, Melissa E., additional, Gärtner, Simone, additional, Han, Bok-Ghee, additional, Havulinna, Aki S., additional, Hayward, Caroline, additional, Hernandez, Dena, additional, Hillege, Hans, additional, Ittermann, Till, additional, Kent, Jack W., additional, Kolcic, Ivana, additional, Laatikainen, Tiina, additional, Lahti, Jari, additional, Leach, Irene Mateo, additional, Lee, Christine G., additional, Lee, Jong-Young, additional, Liu, Tian, additional, Liu, Youfang, additional, Lobbens, Stéphane, additional, Loh, Marie, additional, Lyytikäinen, Leo-Pekka, additional, Medina-Gomez, Carolina, additional, Michaëlsson, Karl, additional, Nalls, Mike A., additional, Nielson, Carrie M., additional, Oozageer, Laticia, additional, Pascoe, Laura, additional, Paternoster, Lavinia, additional, Polašek, Ozren, additional, Ripatti, Samuli, additional, Sarzynski, Mark A., additional, Shin, Chan Soo, additional, Narančić, Nina Smolej, additional, Spira, Dominik, additional, Srikanth, Priya, additional, Steinhagen-Thiessen, Elisabeth, additional, Sung, Yun Ju, additional, Swart, Karin M. A., additional, Taittonen, Leena, additional, Tanaka, Toshiko, additional, Tikkanen, Emmi, additional, van der Velde, Nathalie, additional, van Schoor, Natasja M., additional, Verweij, Niek, additional, Wright, Alan F., additional, Yu, Lei, additional, Zmuda, Joseph M., additional, Eklund, Niina, additional, Forrester, Terrence, additional, Grarup, Niels, additional, Jackson, Anne U., additional, Kristiansson, Kati, additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Lichtner, Peter, additional, Luan, Jian'an, additional, Mahajan, Anubha, additional, Männistö, Satu, additional, Palmer, Cameron D., additional, Ried, Janina S., additional, Scott, Robert A., additional, Stancáková, Alena, additional, Wagner, Peter J., additional, Demirkan, Ayse, additional, Döring, Angela, additional, Gudnason, Vilmundur, additional, Kiel, Douglas P., additional, Kühnel, Brigitte, additional, Mangino, Massimo, additional, Mcknight, Barbara, additional, Menni, Cristina, additional, O'Connell, Jeffrey R., additional, Oostra, Ben A., additional, Shuldiner, Alan R., additional, Song, Kijoung, additional, Vandenput, Liesbeth, additional, van Duijn, Cornelia M., additional, Vollenweider, Peter, additional, White, Charles C., additional, Boehnke, Michael, additional, Boettcher, Yvonne, additional, Cooper, Richard S., additional, Forouhi, Nita G., additional, Gieger, Christian, additional, Grallert, Harald, additional, Hingorani, Aroon, additional, Jørgensen, Torben, additional, Jousilahti, Pekka, additional, Kivimaki, Mika, additional, Kumari, Meena, additional, Laakso, Markku, additional, Langenberg, Claudia, additional, Linneberg, Allan, additional, Luke, Amy, additional, Mckenzie, Colin A., additional, Palotie, Aarno, additional, Pedersen, Oluf, additional, Peters, Annette, additional, Strauch, Konstantin, additional, Tayo, Bamidele O., additional, Wareham, Nicholas J., additional, Bennett, David A., additional, Bertram, Lars, additional, Blangero, John, additional, Blüher, Matthias, additional, Bouchard, Claude, additional, Campbell, Harry, additional, Cho, Nam H., additional, Cummings, Steven R., additional, Czerwinski, Stefan A., additional, Demuth, Ilja, additional, Eckardt, Rahel, additional, Eriksson, Johan G., additional, Ferrucci, Luigi, additional, Franco, Oscar H., additional, Froguel, Philippe, additional, Gansevoort, Ron T., additional, Hansen, Torben, additional, Harris, Tamara B., additional, Hastie, Nicholas, additional, Heliövaara, Markku, additional, Hofman, Albert, additional, Jordan, Joanne M., additional, Jula, Antti, additional, Kähönen, Mika, additional, Kajantie, Eero, additional, Knekt, Paul B., additional, Koskinen, Seppo, additional, Kovacs, Peter, additional, Lehtimäki, Terho, additional, Lind, Lars, additional, Liu, Yongmei, additional, Orwoll, Eric S., additional, Osmond, Clive, additional, Perola, Markus, additional, Pérusse, Louis, additional, Raitakari, Olli T., additional, Rankinen, Tuomo, additional, Rao, D. C., additional, Rice, Treva K., additional, Rivadeneira, Fernando, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Sørensen, Thorkild I. A., additional, Stumvoll, Michael, additional, Tönjes, Anke, additional, Towne, Bradford, additional, Tranah, Gregory J., additional, Tremblay, Angelo, additional, Uitterlinden, André G., additional, van der Harst, Pim, additional, Vartiainen, Erkki, additional, Viikari, Jorma S., additional, Vitart, Veronique, additional, Vohl, Marie-Claude, additional, Völzke, Henry, additional, Walker, Mark, additional, Wallaschofski, Henri, additional, Wild, Sarah, additional, Wilson, James F., additional, Yengo, Loïc, additional, Bishop, D. Timothy, additional, Borecki, Ingrid B., additional, Chambers, John C., additional, Cupples, L. Adrienne, additional, Dehghan, Abbas, additional, Deloukas, Panos, additional, Fatemifar, Ghazaleh, additional, Fox, Caroline, additional, Furey, Terrence S., additional, Franke, Lude, additional, Han, Jiali, additional, Hunter, David J., additional, Karjalainen, Juha, additional, Karpe, Fredrik, additional, Kaplan, Robert C., additional, Kooner, Jaspal S., additional, McCarthy, Mark I., additional, Murabito, Joanne M., additional, Morris, Andrew P., additional, Bishop, Julia A. N., additional, North, Kari E., additional, Ohlsson, Claes, additional, Ong, Ken K., additional, Prokopenko, Inga, additional, Richards, J. Brent, additional, Schadt, Eric E., additional, Spector, Tim D., additional, Widén, Elisabeth, additional, Willer, Cristen J., additional, Yang, Jian, additional, Ingelsson, Erik, additional, Mohlke, Karen L., additional, Hirschhorn, Joel N., additional, Pospisilik, John Andrew, additional, Zillikens, M. Carola, additional, Lindgren, Cecilia, additional, Kilpeläinen, Tuomas Oskari, additional, and Loos, Ruth J. F., additional

Published
2016
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17. Elucidating the genetic architecture of reproductive ageing in the Japanese population.

Author

Momoko Horikoshi, Day, Felix R., Masato Akiyama, Makoto Hirata, Yoichiro Kamatani, Koichi Matsuda, Kazuyoshi Ishigaki, Masahiro Kanai, Wright, Hollis, Toro, Carlos A., Ojeda, Sergio R., Lomniczi, Alejandro, Kubo, Michiaki, Ong, Ken K., and Perry, John R. B.

Subjects
POPULATION aging, PHOSPHOPROTEIN phosphatases, POPULATION genetics, GENE expression, GENE frequency, PROTEIN-tyrosine phosphatase
Abstract

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10-8) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches. [ABSTRACT FROM AUTHOR]

Published
2018
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18. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome

Author

Day, Felix R., primary, Hinds, David A., additional, Tung, Joyce Y., additional, Stolk, Lisette, additional, Styrkarsdottir, Unnur, additional, Saxena, Richa, additional, Bjonnes, Andrew, additional, Broer, Linda, additional, Dunger, David B., additional, Halldorsson, Bjarni V., additional, Lawlor, Debbie A., additional, Laval, Guillaume, additional, Mathieson, Iain, additional, McCardle, Wendy L., additional, Louwers, Yvonne, additional, Meun, Cindy, additional, Ring, Susan, additional, Scott, Robert A., additional, Sulem, Patrick, additional, Uitterlinden, André G., additional, Wareham, Nicholas J., additional, Thorsteinsdottir, Unnur, additional, Welt, Corrine, additional, Stefansson, Kari, additional, Laven, Joop S. E., additional, Ong, Ken K., additional, and Perry, John R. B., additional

Published
2015
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19. Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Author

Lagou, Vasiliki, Mägi, Reedik, Hottenga, Jouke- Jan, Grallert, Harald, Perry, John R. B., Bouatia-Naji, Nabila, Marullo, Letizia, Rybin, Denis, Jansen, Rick, Min, Josine L., Dimas, Antigone S., Ulrich, Anna, Zudina, Liudmila, Gådin, Jesper R., Jiang, Longda, Faggian, Alessia, Bonnefond, Amélie, Fadista, Joao, Stathopoulou, Maria G., and Isaacs, Aaron

Subjects
INSULIN, GLUCOSE, GLUCOSE analysis
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3 [ABSTRACT FROM AUTHOR]

Published
2021
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21. Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

Author

Hollis B, Day FR, Busch AS, Thompson DJ, Soares ALG, Timmers PRHJ, Kwong A, Easton DF, Joshi PK, Timpson NJ, Ong KK, and Perry JRB

Subjects
Adult, Age Factors, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Menarche genetics, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Time Factors, Young Adult, Hair Color genetics, Longevity genetics, Puberty genetics, Sexual Maturation genetics
Abstract

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.

Published
2020
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22. Identification of nine new susceptibility loci for endometrial cancer.

Author

O'Mara TA, Glubb DM, Amant F, Annibali D, Ashton K, Attia J, Auer PL, Beckmann MW, Black A, Bolla MK, Brauch H, Brenner H, Brinton L, Buchanan DD, Burwinkel B, Chang-Claude J, Chanock SJ, Chen C, Chen MM, Cheng THT, Clarke CL, Clendenning M, Cook LS, Couch FJ, Cox A, Crous-Bous M, Czene K, Day F, Dennis J, Depreeuw J, Doherty JA, Dörk T, Dowdy SC, Dürst M, Ekici AB, Fasching PA, Fridley BL, Friedenreich CM, Fritschi L, Fung J, García-Closas M, Gaudet MM, Giles GG, Goode EL, Gorman M, Haiman CA, Hall P, Hankison SE, Healey CS, Hein A, Hillemanns P, Hodgson S, Hoivik EA, Holliday EG, Hopper JL, Hunter DJ, Jones A, Krakstad C, Kristensen VN, Lambrechts D, Marchand LL, Liang X, Lindblom A, Lissowska J, Long J, Lu L, Magliocco AM, Martin L, McEvoy M, Meindl A, Michailidou K, Milne RL, Mints M, Montgomery GW, Nassir R, Olsson H, Orlow I, Otton G, Palles C, Perry JRB, Peto J, Pooler L, Prescott J, Proietto T, Rebbeck TR, Risch HA, Rogers PAW, Rübner M, Runnebaum I, Sacerdote C, Sarto GE, Schumacher F, Scott RJ, Setiawan VW, Shah M, Sheng X, Shu XO, Southey MC, Swerdlow AJ, Tham E, Trovik J, Turman C, Tyrer JP, Vachon C, VanDen Berg D, Vanderstichele A, Wang Z, Webb PM, Wentzensen N, Werner HMJ, Winham SJ, Wolk A, Xia L, Xiang YB, Yang HP, Yu H, Zheng W, Pharoah PDP, Dunning AM, Kraft P, De Vivo I, Tomlinson I, Easton DF, Spurdle AB, and Thompson DJ

Subjects
Alleles, Chromatin chemistry, Female, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Signal Transduction, Biomarkers, Tumor genetics, Endometrial Neoplasms genetics, Genetic Predisposition to Disease
Abstract

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

Published
2018
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23. Rare coding variants and X-linked loci associated with age at menarche.

Author

Lunetta KL, Day FR, Sulem P, Ruth KS, Tung JY, Hinds DA, Esko T, Elks CE, Altmaier E, He C, Huffman JE, Mihailov E, Porcu E, Robino A, Rose LM, Schick UM, Stolk L, Teumer A, Thompson DJ, Traglia M, Wang CA, Yerges-Armstrong LM, Antoniou AC, Barbieri C, Coviello AD, Cucca F, Demerath EW, Dunning AM, Gandin I, Grove ML, Gudbjartsson DF, Hocking LJ, Hofman A, Huang J, Jackson RD, Karasik D, Kriebel J, Lange EM, Lange LA, Langenberg C, Li X, Luan J, Mägi R, Morrison AC, Padmanabhan S, Pirie A, Polasek O, Porteous D, Reiner AP, Rivadeneira F, Rudan I, Sala CF, Schlessinger D, Scott RA, Stöckl D, Visser JA, Völker U, Vozzi D, Wilson JG, Zygmunt M, Boerwinkle E, Buring JE, Crisponi L, Easton DF, Hayward C, Hu FB, Liu S, Metspalu A, Pennell CE, Ridker PM, Strauch K, Streeten EA, Toniolo D, Uitterlinden AG, Ulivi S, Völzke H, Wareham NJ, Wellons M, Franceschini N, Chasman DI, Thorsteinsdottir U, Murray A, Stefansson K, Murabito JM, Ong KK, and Perry JR

Subjects
Adolescent, Adult, Age Factors, Aged, Amides, Cell Cycle Proteins, Chromosomes, Human, X genetics, Codon, Nonsense, Energy Metabolism genetics, Fatty Acids, Female, Gene Frequency, Genes, X-Linked genetics, Genetic Variation, Genotype, Humans, Hypogonadism genetics, Middle Aged, Mutation, Missense, Penetrance, Phenotype, RNA Interference, Signal Transduction genetics, White People genetics, Young Adult, AMP-Activated Protein Kinases genetics, Autoantigens genetics, Immunoglobulins genetics, Laminin genetics, Membrane Proteins genetics, Menarche genetics, Proteins genetics, RNA-Binding Proteins genetics, Receptors, Neurokinin-3 genetics
Abstract

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.

Published
2015
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24. Erratum: Whole-genome sequence-based analysis of thyroid function.

Author

Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ, Mullin BH, Shihab HA, Min J, Walter K, Memari Y, Huang J, Barnes MR, Beilby JP, Charoen P, Danecek P, Dudbridge F, Forgetta V, Greenwood C, Grundberg E, Johnson AD, Hui J, Lim EM, McCarthy S, Muddyman D, Panicker V, Perry JR, Bell JT, Yuan W, Relton C, Gaunt T, Schlessinger D, Abecasis G, Cucca F, Surdulescu GL, Woltersdorf W, Zeggini E, Zheng HF, Toniolo D, Dayan CM, Naitza S, Walsh JP, Spector T, Smith GD, Durbin R, Richards JB, Sanna S, Soranzo N, Timpson NJ, and Wilson SG

Published
2015
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25. Whole-genome sequence-based analysis of thyroid function.

Author

Taylor PN, Porcu E, Chew S, Campbell PJ, Traglia M, Brown SJ, Mullin BH, Shihab HA, Min J, Walter K, Memari Y, Huang J, Barnes MR, Beilby JP, Charoen P, Danecek P, Dudbridge F, Forgetta V, Greenwood C, Grundberg E, Johnson AD, Hui J, Lim EM, McCarthy S, Muddyman D, Panicker V, Perry JR, Bell JT, Yuan W, Relton C, Gaunt T, Schlessinger D, Abecasis G, Cucca F, Surdulescu GL, Woltersdorf W, Zeggini E, Zheng HF, Toniolo D, Dayan CM, Naitza S, Walsh JP, Spector T, Davey Smith G, Durbin R, Richards JB, Sanna S, Soranzo N, Timpson NJ, and Wilson SG

Subjects
3',5'-Cyclic-AMP Phosphodiesterases genetics, 3',5'-Cyclic-AMP Phosphodiesterases metabolism, Cohort Studies, DNA Methylation genetics, Genetic Association Studies, Genomics methods, Humans, Synapsins genetics, Thyroid Gland metabolism, Thyrotropin genetics, Thyroxine genetics, United Kingdom, Synapsins metabolism, Thyroid Gland physiology, Thyrotropin metabolism, Thyroxine metabolism
Abstract

Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10(-9)) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10(-9)) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10(-11)). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.

Published
2015
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