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1. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

Lisa de las Fuentes, Karen L. Schwander, Michael R. Brown, Amy R. Bentley, Thomas W. Winkler, Yun Ju Sung, Patricia B. Munroe, Clint L. Miller, Hugo Aschard, Stella Aslibekyan, Traci M. Bartz, Lawrence F. Bielak, Jin Fang Chai, Ching-Yu Cheng, Rajkumar Dorajoo, Mary F. Feitosa, Xiuqing Guo, Fernando P. Hartwig, Andrea Horimoto, Ivana Kolčić, Elise Lim, Yongmei Liu, Alisa K. Manning, Jonathan Marten, Solomon K. Musani, Raymond Noordam, Sandosh Padmanabhan, Tuomo Rankinen, Melissa A. Richard, Paul M. Ridker, Albert V. Smith, Dina Vojinovic, Alan B. Zonderman, Maris Alver, Mathilde Boissel, Kaare Christensen, Barry I. Freedman, Chuan Gao, Franco Giulianini, Sarah E. Harris, Meian He, Fang-Chi Hsu, Brigitte Kühnel, Federica Laguzzi, Xiaoyin Li, Leo-Pekka Lyytikäinen, Ilja M. Nolte, Alaitz Poveda, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Tamar Sofer, Fumihiko Takeuchi, Bamidele O. Tayo, Peter J. van der Most, Niek Verweij, Erin B. Ware, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Yiqiang Zhan, Najaf Amin, Dan E. Arking, Christie Ballantyne, Eric Boerwinkle, Jennifer A. Brody, Ulrich Broeckel, Archie Campbell, Mickaël Canouil, Xiaoran Chai, Yii-Der Ida Chen, Xu Chen, Kumaraswamy Naidu Chitrala, Maria Pina Concas, Ulf de Faire, Renée de Mutsert, H. Janaka de Silva, Paul S. de Vries, Ahn Do, Jessica D. Faul, Virginia Fisher, James S. Floyd, Terrence Forrester, Yechiel Friedlander, Giorgia Girotto, C. Charles Gu, Göran Hallmans, Sami Heikkinen, Chew-Kiat Heng, Georg Homuth, Steven Hunt, M. Arfan Ikram, David R. Jacobs, Maryam Kavousi, Chiea Chuen Khor, Tuomas O. Kilpeläinen, Woon-Puay Koh, Pirjo Komulainen, Carl D. Langefeld, Jingjing Liang, Kiang Liu, Jianjun Liu, Kurt Lohman, Reedik Mägi, Ani W. Manichaikul, Colin A. McKenzie, Thomas Meitinger, Yuri Milaneschi, Matthias Nauck, Christopher P. Nelson, Jeffrey R. O’Connell, Nicholette D. Palmer, Alexandre C. Pereira, Thomas Perls, Annette Peters, Ozren Polašek, Olli T. Raitakari, Kenneth Rice, Treva K. Rice, Stephen S. Rich, Charumathi Sabanayagam, Pamela J. Schreiner, Xiao-Ou Shu, Stephen Sidney, Mario Sims, Jennifer A. Smith, John M. Starr, Konstantin Strauch, E. Shyong Tai, Kent D. Taylor, Michael Y. Tsai, André G. Uitterlinden, Diana van Heemst, Melanie Waldenberger, Ya-Xing Wang, Wen-Bin Wei, Gregory Wilson, Deng Xuan, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Diane M. Becker, Amélie Bonnefond, Donald W. Bowden, Richard S. Cooper, Ian J. Deary, Jasmin Divers, Tõnu Esko, Paul W. Franks, Philippe Froguel, Christian Gieger, Jost B. Jonas, Norihiro Kato, Timo A. Lakka, Karin Leander, Terho Lehtimäki, Patrik K. E. Magnusson, Kari E. North, Ioanna Ntalla, Brenda Penninx, Nilesh J. Samani, Harold Snieder, Beatrice Spedicati, Pim van der Harst, Henry Völzke, Lynne E. Wagenknecht, David R. Weir, Mary K. Wojczynski, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Claude Bouchard, Daniel I. Chasman, Michele K. Evans, Ervin R. Fox, Vilmundur Gudnason, Caroline Hayward, Bernardo L. Horta, Sharon L. R. Kardia, Jose Eduardo Krieger, Dennis O. Mook-Kanamori, Patricia A. Peyser, Michael M. Province, Bruce M. Psaty, Igor Rudan, Xueling Sim, Blair H. Smith, Rob M. van Dam, Cornelia M. van Duijn, Tien Yin Wong, Donna K. Arnett, Dabeeru C. Rao, James Gauderman, Ching-Ti Liu, Alanna C. Morrison, Jerome I. Rotter, and Myriam Fornage

Subjects
educational attainment, lipids, cholesterol, triglycerides, genome-wide association study, meta-analysis, Genetics, QH426-470
Abstract

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Published
2023
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2. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author

Raymond Noordam, Maxime M. Bos, Heming Wang, Thomas W. Winkler, Amy R. Bentley, Tuomas O. Kilpeläinen, Paul S. de Vries, Yun Ju Sung, Karen Schwander, Brian E. Cade, Alisa Manning, Hugues Aschard, Michael R. Brown, Han Chen, Nora Franceschini, Solomon K. Musani, Melissa Richard, Dina Vojinovic, Stella Aslibekyan, Traci M. Bartz, Lisa de las Fuentes, Mary Feitosa, Andrea R. Horimoto, Marjan Ilkov, Minjung Kho, Aldi Kraja, Changwei Li, Elise Lim, Yongmei Liu, Dennis O. Mook-Kanamori, Tuomo Rankinen, Salman M. Tajuddin, Ashley van der Spek, Zhe Wang, Jonathan Marten, Vincent Laville, Maris Alver, Evangelos Evangelou, Maria E. Graff, Meian He, Brigitte Kühnel, Leo-Pekka Lyytikäinen, Pedro Marques-Vidal, Ilja M. Nolte, Nicholette D. Palmer, Rainer Rauramaa, Xiao-Ou Shu, Harold Snieder, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Correa Adolfo, Christie Ballantyne, Larry Bielak, Nienke R. Biermasz, Eric Boerwinkle, Niki Dimou, Gudny Eiriksdottir, Chuan Gao, Sina A. Gharib, Daniel J. Gottlieb, José Haba-Rubio, Tamara B. Harris, Sami Heikkinen, Raphaël Heinzer, James E. Hixson, Georg Homuth, M. Arfan Ikram, Pirjo Komulainen, Jose E. Krieger, Jiwon Lee, Jingmin Liu, Kurt K. Lohman, Annemarie I. Luik, Reedik Mägi, Lisa W. Martin, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Mike A. Nalls, Jeff O’Connell, Annette Peters, Patricia Peyser, Olli T. Raitakari, Alex P. Reiner, Patrick C. N. Rensen, Treva K. Rice, Stephen S. Rich, Till Roenneberg, Jerome I. Rotter, Pamela J. Schreiner, James Shikany, Stephen S. Sidney, Mario Sims, Colleen M. Sitlani, Tamar Sofer, Konstantin Strauch, Morris A. Swertz, Kent D. Taylor, André G. Uitterlinden, Cornelia M. van Duijn, Henry Völzke, Melanie Waldenberger, Robert B. Wallance, Ko Willems van Dijk, Caizheng Yu, Alan B. Zonderman, Diane M. Becker, Paul Elliott, Tõnu Esko, Christian Gieger, Hans J. Grabe, Timo A. Lakka, Terho Lehtimäki, Kari E. North, Brenda W. J. H. Penninx, Peter Vollenweider, Lynne E. Wagenknecht, Tangchun Wu, Yong-Bing Xiang, Wei Zheng, Donna K. Arnett, Claude Bouchard, Michele K. Evans, Vilmundur Gudnason, Sharon Kardia, Tanika N. Kelly, Stephen B. Kritchevsky, Ruth J. F. Loos, Alexandre C. Pereira, Mike Province, Bruce M. Psaty, Charles Rotimi, Xiaofeng Zhu, Najaf Amin, L. Adrienne Cupples, Myriam Fornage, Ervin F. Fox, Xiuqing Guo, W. James Gauderman, Kenneth Rice, Charles Kooperberg, Patricia B. Munroe, Ching-Ti Liu, Alanna C. Morrison, Dabeeru C. Rao, Diana van Heemst, and Susan Redline

Subjects
Science
Abstract

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

Published
2019
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3. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard-Costa, Anne U. Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian'an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L. Monda, Ilja M. Nolte, Louis Pérusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan T. Smith, Harold Snieder, Alena Stančáková, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J. L. Bakker, Cristina Barlassina, Traci M. Bartz, John Beilby, Claire Bellis, Richard N. Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L. Bonnycastle, Stefan R. Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W. K. Chiang, Peter S. Chines, Francis S Collins, Fracensco Cucca, L Adrienne Cupples, Francesca D’Avila, Eco J .C. de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G. Eriksson, Aliki-Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G. Forouhi, Nele Friedrich, Anette Prior Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A. Hartman, Maija Hassinen, Nicholas Hastie, Andrew Tym Hattersley, Aki S. Havulinna, Markku Heliövaara, Hans Hillege, Albert Hofman, Oddgeir Holmen, Georg Homuth, Jouke-Jan Hottenga, Jennie Hui, Lise Lotte Husemoen, Pirro G. Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Alan L. James, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Johanne Marie Justesen, Anne E. Justice, Mika Kähönen, Maria Karaleftheri, Kay Tee Khaw, Sirkka M. Keinanen-Kiukaanniemi, Leena Kinnunen, Paul B. Knekt, Heikki A. Koistinen, Ivana Kolcic, Ishminder K. Kooner, Seppo Koskinen, Peter Kovacs, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alexandra M. Lewin, Peter Lichtner, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L. McArdle, Barbara Mcknight, Karen L. Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E. Montasser, Andrew P. Morris, Gabriele Müller, Arthur W. Musk, Narisu Narisu, Ken K. Ong, Ben A. Oostra, Clive Osmond, Aarno Palotie, James S. Pankow, Lavinia Paternoster, Brenda W. Penninx, Irene Pichler, Maria G. Pilia, Ozren Polašek, Peter P. Pramstaller, Olli T Raitakari, Tuomo Rankinen, D. C. Rao, Nigel W. Rayner, Rasmus Ribel-Madsen, Treva K. Rice, Marcus Richards, Paul M. Ridker, Fernando Rivadeneira, Kathy A. Ryan, Serena Sanna, Mark A. Sarzynski, Salome Scholtens, Robert A. Scott, Sylvain Sebert, Lorraine Southam, Thomas Hempel Sparsø, Valgerdur Steinthorsdottir, Kathleen Stirrups, Ronald P. Stolk, Konstantin Strauch, Heather M. Stringham, Morris A. Swertz, Amy J. Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma S. Viikari, Veronique Vitart, Marie-Claude Vohl, Judith M. Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W. Winkler, Alan F. Wright, Laura M. Yerges-Armstrong, Jing Hua Zhao, M. Carola Zillikens, Dorret I. Boomsma, Claude Bouchard, John C. Chambers, Daniel I. Chasman, Daniele Cusi, Ron T. Gansevoort, Christian Gieger, Torben Hansen, Andrew A. Hicks, Frank Hu, Kristian Hveem, Marjo-Riitta Jarvelin, Eero Kajantie, Jaspal S. Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Lyle J. Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M. Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter E. H. Schwarz, Alan R. Shudiner, Jan H. Smit, Thorkild I. A. Sørensen, Timothy D. Spector, Kari Stefansson, Michael Stumvoll, Angelo Tremblay, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Uwe Völker, Peter Vollenweider, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Eleftheria Zeggini, Goncalo R. Abecasis, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Cornelia M. van Duijn, Caroline Fox, Leif C. Groop, Iris M. Heid, David J. Hunter, Robert C. Kaplan, Mark I. McCarthy, Kari E. North, Jeffrey R. O'Connell, David Schlessinger, Unnur Thorsteinsdottir, David P. Strachan, Timothy Frayling, Joel N. Hirschhorn, Martina Müller-Nurasyid, and Ruth J. F. Loos

Subjects
Science
Abstract

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Published
2016
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4. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author

Tuomas O. Kilpeläinen, Jayne F. Martin Carli, Alicja A. Skowronski, Qi Sun, Jennifer Kriebel, Mary F Feitosa, Åsa K. Hedman, Alexander W. Drong, James E. Hayes, Jinghua Zhao, Tune H. Pers, Ursula Schick, Niels Grarup, Zoltán Kutalik, Stella Trompet, Massimo Mangino, Kati Kristiansson, Marian Beekman, Leo-Pekka Lyytikäinen, Joel Eriksson, Peter Henneman, Jari Lahti, Toshiko Tanaka, Jian’an Luan, Fabiola Del Greco M, Dorota Pasko, Frida Renström, Sara M. Willems, Anubha Mahajan, Lynda M. Rose, Xiuqing Guo, Yongmei Liu, Marcus E. Kleber, Louis Pérusse, Tom Gaunt, Tarunveer S. Ahluwalia, Yun Ju Sung, Yolande F. Ramos, Najaf Amin, Antoinette Amuzu, Inês Barroso, Claire Bellis, John Blangero, Brendan M. Buckley, Stefan Böhringer, Yii-Der I Chen, Anton J. N. de Craen, David R. Crosslin, Caroline E. Dale, Zari Dastani, Felix R. Day, Joris Deelen, Graciela E. Delgado, Ayse Demirkan, Francis M. Finucane, Ian Ford, Melissa E. Garcia, Christian Gieger, Stefan Gustafsson, Göran Hallmans, Susan E. Hankinson, Aki S Havulinna, Christian Herder, Dena Hernandez, Andrew A. Hicks, David J. Hunter, Thomas Illig, Erik Ingelsson, Andreea Ioan-Facsinay, John-Olov Jansson, Nancy S. Jenny, Marit E. Jørgensen, Torben Jørgensen, Magnus Karlsson, Wolfgang Koenig, Peter Kraft, Joanneke Kwekkeboom, Tiina Laatikainen, Karl-Heinz Ladwig, Charles A. LeDuc, Gordon Lowe, Yingchang Lu, Pedro Marques-Vidal, Christa Meisinger, Cristina Menni, Andrew P. Morris, Richard H. Myers, Satu Männistö, Mike A. Nalls, Lavinia Paternoster, Annette Peters, Aruna D. Pradhan, Tuomo Rankinen, Laura J. Rasmussen-Torvik, Wolfgang Rathmann, Treva K. Rice, J Brent Richards, Paul M. Ridker, Naveed Sattar, David B. Savage, Stefan Söderberg, Nicholas J. Timpson, Liesbeth Vandenput, Diana van Heemst, Hae-Won Uh, Marie-Claude Vohl, Mark Walker, Heinz-Erich Wichmann, Elisabeth Widén, Andrew R. Wood, Jie Yao, Tanja Zeller, Yiying Zhang, Ingrid Meulenbelt, Margreet Kloppenburg, Arne Astrup, Thorkild I. A. Sørensen, Mark A. Sarzynski, D. C. Rao, Pekka Jousilahti, Erkki Vartiainen, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Eero Kajantie, Clive Osmond, Aarno Palotie, Johan G. Eriksson, Markku Heliövaara, Paul B. Knekt, Seppo Koskinen, Antti Jula, Markus Perola, Risto K. Huupponen, Jorma S. Viikari, Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Dan Mellström, Mattias Lorentzon, Juan P. Casas, Stefanie Bandinelli, Winfried März, Aaron Isaacs, Ko W. van Dijk, Cornelia M. van Duijn, Tamara B. Harris, Claude Bouchard, Matthew A. Allison, Daniel I. Chasman, Claes Ohlsson, Lars Lind, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, Luigi Ferrucci, Timothy M. Frayling, Peter P. Pramstaller, Ingrid B. Borecki, Dawn M. Waterworth, Sven Bergmann, Gérard Waeber, Peter Vollenweider, Henrik Vestergaard, Torben Hansen, Oluf Pedersen, Frank B. Hu, P Eline Slagboom, Harald Grallert, Tim D. Spector, J.W. Jukema, Robert J. Klein, Erik E Schadt, Paul W. Franks, Cecilia M. Lindgren, Rudolph L. Leibel, and Ruth J. F. Loos

Subjects
Science
Abstract

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

Published
2016
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5. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

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

Subjects
Science
Abstract

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Published
2016
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6. The HERITAGE Family Study: A Review of the Effects of Exercise Training on Cardiometabolic Health, with Insights into Molecular Transducers

Author

MARK A. SARZYNSKI, TREVA K. RICE, JEAN-PIERRE DESPRÉS, LOUIS PÉRUSSE, ANGELO TREMBLAY, PHILIP R. STANFORTH, ANDRÉ TCHERNOF, JACOB L. BARBER, FRANCESCO FALCIANI, CLARY CLISH, JEREMY M. ROBBINS, SUJOY GHOSH, ROBERT E. GERSZTEN, ARTHUR S. LEON, JAMES S. SKINNER, D. C. RAO, and CLAUDE BOUCHARD

Subjects
Proteomics, Cardiorespiratory Fitness, Cardiovascular Diseases, Hemodynamics, Computational Biology, Humans, Metabolomics, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, Genomics, Exercise
Abstract

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study.

Published
2022

7. Abstract P263: The Associations of Epithelial Sodium Channel Genes with Blood Pressure Changes and Hypertension Incidence: the GenSalt Study

Author

Tanika N Kelly, Xueli Yang, Dabeeru C Rao, Dongfeng Gu, James E Hixson, Treva K Rice, Depei Liu, Lawrence C Shimmin, and Jiang He

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

We examined the associations of common variants in ENaC genes with BP changes and hypertension incidence in a longitudinal family study. A total of 2755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eligible for the current study. The average of nine BP measurements obtained using a random-zero sphygmomanometer at the baseline and each of two follow-up visits were used for the current analysis. The associations of 43 tag-SNPs in ENaC genes with BP changes and hypertension incidence were assessed using mixed models to account for the correlations of repeated measures among individuals and within families. A genotype by time interaction term was used to model differences in BP change according to genotype over time. The false discovery rate (FDR) method was used to adjust for multiple testing. During an average of 7.4 years follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of participants developed hypertension. Multiple variants in ENaC genes were significantly associated with longitudinal changes in SBP after adjustment for multiple testing, including SCNN1A SNP rs11064153 ( P interaction = 5.8х10 -4 ; FDR-Q = 0.01); SCNN1G SNPs rs4299163 ( P interaction = 0.011; FDR-Q = 0.05) and rs4401050 ( P interaction = 0.001; FDR-Q = 0.01); and SCNN1B SNP rs1004749 ( P interaction = 0.006; FDR-Q = 0.03). Similar but not significant trends were observed for the associations between both rs11064153 and rs4401050 and DBP changes ( P interaction = 0.024 and 0.005, respectively; FDR-Q = 0.41 and 0.17, respectively) and between rs11604153 and hypertension incidence ( P = 0.017; FDR-Q = 0.19). Our findings indicate that ENaC genes may contribute to longitudinal BP changes in the Han Chinese population. Replication of these findings is warranted.

Published
2014
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8. Abstract MP15: Single And Joint Associations Of Genetic Variants In The Serum/glucocorticoid Regulated Kinase (sgk) Genes With Blood Pressure Responses To Sodium Intake: The Gensalt Study

Author

Changwei Li, Xueli Yang, Jiang He, James E Hixson, Dongfeng Gu, Dabeeru C Rao, Cashell E Jaquish, Treva K Rice, De-Pei Liu, Lawrence C Shimmin, Jianfeng Huang, Fanghong Lu, Jie Cao, Shen Chong, Xiangfeng Lu, and Tanika N Kelly

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Serum and glucocorticoid regulated kinase (SGK) plays a critical role in the regulation of renal sodium transport. We examined the association between SGK genes and salt sensitivity of blood pressure (BP) using single-marker and gene-based association analyses. Methods: A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium intervention (307.8 mmol sodium/day) was conducted among 1,906 Chinese participants. BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Additive associations between each SNP and salt-sensitivity phenotypes were assessed using a mixed linear regression model to account for family dependencies. Gene-based analyses were conducted using the truncated p-value method. The Bonferroni-method was used to adjust for multiple testing in all analyses. Results: In single-marker association analyses, SGK1 marker rs2758151 was significantly associated with diastolic BP (DBP) response to high-sodium intervention (P=0.0010). DBP responses (95% confidence interval) to high-sodium intervention for genotypes C/C, C/T, and T/T were 2.04 (1.57 to 2.52), 1.79 (1.42 to 2.16), and 0.85 (0.30 to 1.41) mmHg, respectively. Similar non-significant trends were observed for SBP and MAP responses (P=0.15 and 0.0026, respectively). In addition, gene-based analyses demonstrated significant associations between SGK1 and SBP, DBP and MAP responses to high sodium intervention (P=0.0002, 0.0076, and 0.00001, respectively). Neither SGK2 nor SGK3 were associated with the salt-sensitivity phenotypes in single-maker and gene-based analyses. Conclusions: The current study identified single-marker and gene-based association of the SGK1 gene and BP salt-sensitivity in the Han Chinese population. Further studies are warranted to identify causal SGK1 gene variants.

Published
2014
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9. Three ontologies to define phenotype measurement data

Author

Mary eShimoyama, Rajni eNigam, Leslie Sanders McIntosh, Rakesh eNagarajan, Treva K Rice, D.C. eRao, and Melinda R. Dwinell

Subjects
0303 health sciences, lcsh:QH426-470, Computer science, phenotype, Ontology-based data integration, Ontology (information science), computer.software_genre, Phenotype, Data science, Rat Genome Database, Open Biomedical Ontologies, 03 medical and health sciences, lcsh:Genetics, 0302 clinical medicine, Resource (project management), Genetics, Molecular Medicine, ontology, computer, Protocol (object-oriented programming), 030217 neurology & neurosurgery, Genetics (clinical), 030304 developmental biology, Data integration, Original Research
Abstract

There is an increasing need to integrate phenotype measurement data across studies for both human studies and those involving model organisms. Current practices allow researchers to access only those data involved in a single experiment or multiple experiments utilizing the same protocol. To standardize the elements of phenotype measurement records, three ontologies were created: Clinical Measurement Ontology, Measurement Method Ontology and Experimental Condition Ontology. These ontologies provide the framework for integration of rat phenotype data from multiple studies into a single resource as well as facilitate data integration from multiple human epidemiological studies into a centralized repository. An ontology based framework for phenotype measurement data affords the ability to successfully integrate vital phenotype data into critical resources, regardless of underlying technological structures allowing the user to easily query and retrieve data from multiple studies.

Published
2012

10. Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure

Author

Dongfeng, Gu, Tanika N, Kelly, James E, Hixson, Jing, Chen, Depei, Liu, Ji-chun, Chen, Dabeeru C, Rao, Jianjun, Mu, Jixiang, Ma, Cashell E, Jaquish, Treva K, Rice, Charles, Gu, L Lee, Hamm, Paul K, Whelton, and Jiang, He

Subjects
Adult, Male, China, Adolescent, Genetic Variation, Blood Pressure, Middle Aged, Polymorphism, Single Nucleotide, Article, Renin-Angiotensin System, Young Adult, Surveys and Questionnaires, Humans, Female, Sodium Chloride, Dietary, Alleles
Abstract

To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt sensitivity of blood pressure (BP).A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was conducted among 1906 participants living in a rural region of north China where habitual sodium intake is high. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer.DBP and mean arterial pressure responses increased with the number of rs4524238 A alleles in the angiotensin II receptor type 1 gene. For example, mean DBP responses (95% confidence interval) among those with genotypes G/G, G/A, and A/A were -2.53 (-2.89 to -2.18), -3.49 (-4.13 to -2.86), and -5.78 (-9.51 to -2.06) mmHg, respectively, following the low-sodium intervention (P=0.0008). Carriers of the rare A allele of rs5479 in the hydroxysteroid (11-beta) dehydrogenase 2 gene had decreased DBP responses to low sodium (P=0.00004). Those with the C/A and C/C genotypes had DBP responses of -0.70 (-6.62 to 5.22) and -2.71 (-4.88 to -0.54) mmHg, respectively. X chromosome renin-binding protein gene markers rs1557501 and rs2269372 were associated with SBP response to low sodium in men (P=0.00004 and 0.0001, respectively). SBP responses (95% confidence interval) were -6.13 (-6.68 to -5.58) versus -4.07 (-4.88 to -3.26) and -6.04 (-6.57 to -5.52) versus -3.94 (-4.90 to -2.99) mmHg among men with major versus those with minor alleles of rs1557501 and rs2269372, respectively. Haplotype analyses of these genes supported our single-marker findings.We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake.

Published
2010

11. Familial resemblance and heritability

Author

Treva K, Rice

Subjects
Multifactorial Inheritance, Quantitative Trait, Heritable, Humans, Family
Abstract

Familial resemblance arises when family members are more similar than unrelated pairs of individuals, and may be estimated in terms of correlations or covariances among family members. Multifactorial heritability (or generalized heritability) quantifies the strength of the familial resemblance and represents the percentage of variance that is due to all additive familial effects including additive genetic and those of the familial environment. However, the traditional concept of heritability, which may be more appropriately called the genetic heritability, represents only the percentage of phenotypic variance due to additive genetic effects. Resolving the various sources of familial resemblance entails other issues. For example, there may be major gene effects that are largely or entirely nonadditive, temporal or developmental trends, and gene-gene (epistasis) and gene-environment interactions. The design of a family study determines which of these sources are resolvable. For example, in nuclear families consisting of parents and offspring, the genetic and familial environmental effects are not resolvable because these relatives share both genes and environments. However, extended pedigree and twin and adoption designs allow separation of the heritable effects and, possibly, more complex etiologies, including interactions. Various factors affect the estimation and interpretability of heritabilities, for example, assumptions regarding linearity and additivity, assortative mating, and the underlying distribution of the data. Nonnormality of the data can lead to errors in hypothesis testing, although it yields reasonably unbiased estimates. Fortunately, these and other complications can be directly modeled in many of the sophisticated software packages available today in genetic epidemiology.

Published
2008

12. Methods for handling multiple testing

Author

Treva K, Rice, Nicholas J, Schork, and D C, Rao

Subjects
Genetic Markers, Genetic Techniques, Genotype, Humans, False Positive Reactions, False Negative Reactions
Abstract

The availability of high-throughput genotyping technologies and massive amounts of marker data for testing genetic associations is a dual-edged sword. On one side is the possibility that the causative gene (or a closely linked one) will be found from among those tested for association, but on the other testing, many loci for association creates potential false positive results and the need to accommodate the multiple testing problem. Traditional solutions involve correcting each test using adjustments such as a Bonferroni correction. This worked well in settings involving a few tests (e.g., 10-20, as is typical for candidate gene studies) and even when the number of tests was somewhat larger (e.g., a few hundred as in genome-wide microsatellite scans). However, the current dense single nucleotide polymorphism (SNP) and/or whole-genome association (WGA) studies often consider several thousand to upwards of 500,000 and 1 million SNPs. In these settings, a Bonferroni correction is not practical as it does not take into account correlations between the tests due to linkage disequilibrium and hence can be too conservative. The effect sizes of susceptibility alleles will rarely (if ever) reach the required level of significance in WGA studies if a Bonferroni correction is used, and the number of false negatives is likely to be large. Thus, one of the burning methodological issues in contemporary genetic epidemiology and statistical genetics is how to balance false positives and false negatives in large-scale association studies. This chapter reviews developments in this area from both historical and current perspectives.

Published
2008

13. Smoking and Genetic Risk Variation Across Populations of European, Asian, and African American Ancestry-A Meta-Analysis of Chromosome 15q25

Author

Li-Shiun Chen, Nancy L. Saccone, Robert C. Culverhouse, Paige M. Bracci, Chien-Hsiun Chen, Nicole Dueker, Younghun Han, Hongyan Huang, Guangfu Jin, Takashi Kohno, Jennie Z. Ma, Thomas R. Przybeck, Alan R. Sanders, Jennifer A. Smith, Yun Ju Sung, Angie S. Wenzlaff, Chen Wu, Dankyu Yoon, Ying-Ting Chen, Yu-Ching Cheng, Yoon Shin Cho, Sean P. David, Jubao Duan, Charles B. Eaton, Helena Furberg, Alison M. Goate, Dongfeng Gu, Helen M. Hansen, Sarah Hartz, Zhibin Hu, Young Jin Kim, Steven J. Kittner, Douglas F. Levinson, Thomas H. Mosley, Thomas J. Payne, D. C. Rao, John P. Rice, Treva K. Rice, Tae-Hwi Schwantes-An, Sanjay S. Shete, Jianxin Shi, Margaret R. Spitz, Yan V. Sun, Fuu-Jen Tsai, Jen C. Wang, Margaret R. Wrensch, Hong Xian, Pablo V. Gejman, Jiang He, Steven C. Hunt, Sharon L. Kardia, Ming D. Li, Dongxin Lin, Braxton D. Mitchell, Taesung Park, Ann G. Schwartz, Hongbing Shen, John K. Wiencke, Jer-Yuarn Wu, Jun Yokota, Christopher I. Amos, and Laura J. Bierut

Subjects
Epidemiology, Genetics (clinical)
Published
2012
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15. Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author

Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos

Subjects
Genetics, QH426-470
Abstract

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].

Published
2016
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16. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Author

Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, Su Chu, Jacek Czajkowski, Tõnu Esko, Tove Fall, Tuomas O Kilpeläinen, Yingchang Lu, Reedik Mägi, Evelin Mihailov, Tune H Pers, Sina Rüeger, Alexander Teumer, Georg B Ehret, Teresa Ferreira, Nancy L Heard-Costa, Juha Karjalainen, Vasiliki Lagou, Anubha Mahajan, Michael D Neinast, Inga Prokopenko, Jeannette Simino, Tanya M Teslovich, Rick Jansen, Harm-Jan Westra, Charles C White, Devin Absher, Tarunveer S Ahluwalia, Shafqat Ahmad, Eva Albrecht, Alexessander Couto Alves, Jennifer L Bragg-Gresham, Anton J M de Craen, Joshua C Bis, Amélie Bonnefond, Gabrielle Boucher, Gemma Cadby, Yu-Ching Cheng, Charleston W K Chiang, Graciela Delgado, Ayse Demirkan, Nicole Dueker, Niina Eklund, Gudny Eiriksdottir, Joel Eriksson, Bjarke Feenstra, Krista Fischer, Francesca Frau, Tessel E Galesloot, Frank Geller, Anuj Goel, Mathias Gorski, Tanja B Grammer, Stefan Gustafsson, Saskia Haitjema, Jouke-Jan Hottenga, Jennifer E Huffman, Anne U Jackson, Kevin B Jacobs, Åsa Johansson, Marika Kaakinen, Marcus E Kleber, Jari Lahti, Irene Mateo Leach, Benjamin Lehne, Youfang Liu, Ken Sin Lo, Mattias Lorentzon, Jian'an Luan, Pamela A F Madden, Massimo Mangino, Barbara McKnight, Carolina Medina-Gomez, Keri L Monda, May E Montasser, Gabriele Müller, Martina Müller-Nurasyid, Ilja M Nolte, Kalliope Panoutsopoulou, Laura Pascoe, Lavinia Paternoster, Nigel W Rayner, Frida Renström, Federica Rizzi, Lynda M Rose, Kathy A Ryan, Perttu Salo, Serena Sanna, Hubert Scharnagl, Jianxin Shi, Albert Vernon Smith, Lorraine Southam, Alena Stančáková, Valgerdur Steinthorsdottir, Rona J Strawbridge, Yun Ju Sung, Ioanna Tachmazidou, Toshiko Tanaka, Gudmar Thorleifsson, Stella Trompet, Natalia Pervjakova, Jonathan P Tyrer, Liesbeth Vandenput, Sander W van der Laan, Nathalie van der Velde, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Efthymia Vlachopoulou, Lindsay L Waite, Sophie R Wang, Zhaoming Wang, Sarah H Wild, Christina Willenborg, James F Wilson, Andrew Wong, Jian Yang, Loïc Yengo, Laura M Yerges-Armstrong, Lei Yu, Weihua Zhang, Jing Hua Zhao, Ehm A Andersson, Stephan J L Bakker, Damiano Baldassarre, Karina Banasik, Matteo Barcella, Cristina Barlassina, Claire Bellis, Paola Benaglio, John Blangero, Matthias Blüher, Fabrice Bonnet, Lori L Bonnycastle, Heather A Boyd, Marcel Bruinenberg, Aron S Buchman, Harry Campbell, Yii-Der Ida Chen, Peter S Chines, Simone Claudi-Boehm, John Cole, Francis S Collins, Eco J C de Geus, Lisette C P G M de Groot, Maria Dimitriou, Jubao Duan, Stefan Enroth, Elodie Eury, Aliki-Eleni Farmaki, Nita G Forouhi, Nele Friedrich, Pablo V Gejman, Bruna Gigante, Nicola Glorioso, Alan S Go, Omri Gottesman, Jürgen Gräßler, Harald Grallert, Niels Grarup, Yu-Mei Gu, Linda Broer, Annelies C Ham, Torben Hansen, Tamara B Harris, Catharina A Hartman, Maija Hassinen, Nicholas Hastie, Andrew T Hattersley, Andrew C Heath, Anjali K Henders, Dena Hernandez, Hans Hillege, Oddgeir Holmen, Kees G Hovingh, Jennie Hui, Lise L Husemoen, Nina Hutri-Kähönen, Pirro G Hysi, Thomas Illig, Philip L De Jager, Shapour Jalilzadeh, Torben Jørgensen, J Wouter Jukema, Markus Juonala, Stavroula Kanoni, Maria Karaleftheri, Kay Tee Khaw, Leena Kinnunen, Steven J Kittner, Wolfgang Koenig, Ivana Kolcic, Peter Kovacs, Nikolaj T Krarup, Wolfgang Kratzer, Janine Krüger, Diana Kuh, Meena Kumari, Theodosios Kyriakou, Claudia Langenberg, Lars Lannfelt, Chiara Lanzani, Vaneet Lotay, Lenore J Launer, Karin Leander, Jaana Lindström, Allan Linneberg, Yan-Ping Liu, Stéphane Lobbens, Robert Luben, Valeriya Lyssenko, Satu Männistö, Patrik K Magnusson, Wendy L McArdle, Cristina Menni, Sigrun Merger, Lili Milani, Grant W Montgomery, Andrew P Morris, Narisu Narisu, Mari Nelis, Ken K Ong, Aarno Palotie, Louis Pérusse, Irene Pichler, Maria G Pilia, Anneli Pouta, Myriam Rheinberger, Rasmus Ribel-Madsen, Marcus Richards, Kenneth M Rice, Treva K Rice, Carlo Rivolta, Veikko Salomaa, Alan R Sanders, Mark A Sarzynski, Salome Scholtens, Robert A Scott, William R Scott, Sylvain Sebert, Sebanti Sengupta, Bengt Sennblad, Thomas Seufferlein, Angela Silveira, P Eline Slagboom, Jan H Smit, Thomas H Sparsø, Kathleen Stirrups, Ronald P Stolk, Heather M Stringham, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Emmanouil Tsafantakis, Peter J van der Most, Uwe Völker, Marie-Claude Vohl, Judith M Vonk, Melanie Waldenberger, Ryan W Walker, Roman Wennauer, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Alan F Wright, M Carola Zillikens, Suzanne C van Dijk, Natasja M van Schoor, Folkert W Asselbergs, Paul I W de Bakker, Jacques S Beckmann, John Beilby, David A Bennett, Richard N Bergman, Sven Bergmann, Carsten A Böger, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, John C Chambers, Stephen J Chanock, Daniel I Chasman, Francesco Cucca, Daniele Cusi, George Dedoussis, Jeanette Erdmann, Johan G Eriksson, Denis A Evans, Ulf de Faire, Martin Farrall, Luigi Ferrucci, Ian Ford, Lude Franke, Paul W Franks, Philippe Froguel, Ron T Gansevoort, Christian Gieger, Henrik Grönberg, Vilmundur Gudnason, Ulf Gyllensten, Per Hall, Anders Hamsten, Pim van der Harst, Caroline Hayward, Markku Heliövaara, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Albert Hofman, Frank Hu, Heikki V Huikuri, Kristian Hveem, Alan L James, Joanne M Jordan, Antti Jula, Mika Kähönen, Eero Kajantie, Sekar Kathiresan, Lambertus A L M Kiemeney, Mika Kivimaki, Paul B Knekt, Heikki A Koistinen, Jaspal S Kooner, Seppo Koskinen, Johanna Kuusisto, Winfried Maerz, Nicholas G Martin, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Guillaume Lettre, Douglas F Levinson, Lars Lind, Marja-Liisa Lokki, Pekka Mäntyselkä, Mads Melbye, Andres Metspalu, Braxton D Mitchell, Frans L Moll, Jeffrey C Murray, Arthur W Musk, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Ben A Oostra, Lyle J Palmer, James S Pankow, Gerard Pasterkamp, Nancy L Pedersen, Oluf Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P Pramstaller, Bruce M Psaty, Lu Qi, Thomas Quertermous, Olli T Raitakari, Tuomo Rankinen, Rainer Rauramaa, Paul M Ridker, John D Rioux, Fernando Rivadeneira, Jerome I Rotter, Igor Rudan, Hester M den Ruijter, Juha Saltevo, Naveed Sattar, Heribert Schunkert, Peter E H Schwarz, Alan R Shuldiner, Juha Sinisalo, Harold Snieder, Thorkild I A Sørensen, Tim D Spector, Jan A Staessen, Bandinelli Stefania, Unnur Thorsteinsdottir, Michael Stumvoll, Jean-Claude Tardif, Elena Tremoli, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, André L M Verbeek, Sita H Vermeulen, Jorma S Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Gérard Waeber, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, Eleftheria Zeggini, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Aravinda Chakravarti, Deborah J Clegg, L Adrienne Cupples, Penny Gordon-Larsen, Cashell E Jaquish, D C Rao, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Sonja I Berndt, Michael Boehnke, Panos Deloukas, Caroline S Fox, Leif C Groop, David J Hunter, Erik Ingelsson, Robert C Kaplan, Mark I McCarthy, Karen L Mohlke, Jeffrey R O'Connell, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Joel N Hirschhorn, Cecilia M Lindgren, Iris M Heid, Kari E North, Ingrid B Borecki, Zoltán Kutalik, and Ruth J F Loos

Subjects
Genetics, QH426-470
Abstract

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR

Published
2015
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17. Variation in genes that regulate blood pressure are associated with glomerular filtration rate in Chinese.

Author

May E Montasser, Lawrence C Shimmin, Dongfeng Gu, Jing Chen, Charles Gu, Tanika N Kelly, Cashell E Jaquish, Treva K Rice, Dabeeru C Rao, Jie Cao, Jichun Chen, De-PeLiu, Paul K Whelton, Lotuce Lee Hamm, Jiang He, and James E Hixson

Subjects
Medicine, Science
Abstract

Chronic kidney disease (CKD) can be a consequence of diabetes, hypertension, immunologic disorders, and other exposures, as well as genetic factors that are still largely unknown. Glomerular filtration rate (GFR), which is widely used to measure kidney function, has a heritability ranging from 25% to 75%, but only 1.5% of this heritability is explained by genetic loci that have been identified to date. In this study we tested for associations between GFR and 234 SNPs in 26 genes from pathways of blood pressure regulation in 3,025 rural Chinese participants of the "Genetic Epidemiology Network of Salt Sensitivity" (GenSalt) study. We estimated GFR (eGFR) using baseline serum creatinine measurements obtained prior to dietary intervention. We identified significant associations between eGFR and 12 SNPs in 6 genes (ACE, ADD1, AGT, GRK4, HSD11B1, and SCNN1G). The cumulative effect of the protective alleles was an increase in mean eGFR of 4 mL/min per 1.73 m2, while the cumulative effect of the risk alleles was a decrease in mean eGFR of 3 mL/min per 1.73 m2. In addition, we identified a significant interaction between SNPs in CYP11B1 and ADRB2. We have identified common variants in genes from pathways that regulate blood pressure and influence kidney function as measured by eGFR, providing new insights into the genetic determinants of kidney function. Complex genetic effects on kidney function likely involve interactions among genes as we observed for CYP11B1 and ADRB2.

Published
2014
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18. Genome-wide detection of allele specific copy number variation associated with insulin resistance in African Americans from the HyperGEN study.

Author

Marguerite R Irvin, Nathan E Wineinger, Treva K Rice, Nicholas M Pajewski, Edmond K Kabagambe, Charles C Gu, Jim Pankow, Kari E North, Jemma B Wilk, Barry I Freedman, Nora Franceschini, Uli Broeckel, Hemant K Tiwari, and Donna K Arnett

Subjects
Medicine, Science
Abstract

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10(-7)≤P≤1.1*10(-5)) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10(-6)). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P

Published
2011
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