Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

著者: Tuomas O. Kilpeläinen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, Daniel I. Chasman, Alisa K. Manning, Ιωάννα Ντάλλα, Hugues Aschard, Michael R. Brown, Lisa de las Fuentes, Nora Franceschini, Xiuqing Guo, Dina Vojinović, Stella Aslibekyan, Mary F. Feitosa, Minjung Kho, Solomon K. Musani, Melissa A. Richard, Heming Wang, Zhe Wang, Traci M. Bartz, Lawrence F. Bielak, Archie Campbell, Rajkumar Dorajoo, Virginia Fisher, Fernando Pires Hartwig, Andréa R. V. R. Horimoto, Changwei Li, Kurt K. Lohman, Jonathan Marten, Xueling Sim, Albert V. Smith, Salman M. Tajuddin, Maris Alver, Marzyeh Amini, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Εvangelos Εvangelou, Chuan Gao, Mariaelisa Graff, Sarah E. Harris, Meian He, Fang‐Chi Hsu, Anne Jackson, Jing Hua Zhao, Aldi T. Kraja, Brigitte Kühnel, Federica Laguzzi, Leo‐Pekka Lyytikäinen, Ilja M. Nolte, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Rico Rueedi, Heather M. Stringham, Fumihiko Takeuchi, Peter J. van der Most, Tibor V. Varga, Niek Verweij, Erin B. Ware, Wanqing Wen, Xiaoyin Li, Lisa R. Yanek, Najaf Amin, Donna K. Arnett, Eric Boerwinkle, Marco Brumat, Brian E. Cade, Mickaël Canouil, Yii‐Der Ida Chen, Maria Pina Concas, John Connell, Renée de Mutsert, Hernan Silva, Paul S. de Vries, Ayşe Demirkan, Jingzhong Ding, Charles B. Eaton, Jessica D. Faul, Yechiel Friedlander, Kelley Pettee Gabriel, Mohsen Ghanbari, Franco Giulianini, C. Charles Gu, Dongfeng Gu, Tamara B. Harris, Jiang He, Sami Heikkinen, Chew‐Kiat Heng, Steven C. Hunt, M. Arfan Ikram, Jost B. Jonas, Woon‐Puay Koh, Pirjo Komulainen, José Eduardo Krieger, Stephen B. Kritchevsky, Zoltán Kutalik, Johanna Kuusisto, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Karin Leander, Rozenn N. Lemaître, Cora E. Lewis, Jingjing Liang, Lifelines Cohort Study, Behrooz Z. Alizadeh, H. Marike Boezen, Lude Franke, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H. R. Wolffenbuttel, Cisca Wijmenga, Jianjun Liu, Reedik Mägi, Ani Manichaikul, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Karen L Mohlke, Thomas H Mosley, Alison D. Murray, Mike A. Nalls, Ei-Ei Khaing Nang, Christopher P. Nelson, Sotoodehnia Nona, Jill M. Norris, Chiamaka Nwuba, Jeff O’Connell, Nicholette D Palmer, George Papanicolau, Raha Pazoki, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Ozren Polašek, David J. Porteous, Alaitz Poveda, Olli T Raitakari, Stephen S. Rich, Neil Risch, Jennifer G. Robinson, Lynda M. Rose, Igor Rudan, Pamela J. Schreiner, Robert A Scott, Stephen Sidney, Mario Sims, Jennifer A. Smith, Harold Snieder, Tamar Sofer, John M Starr, Barbara Sternfeld, Konstantin Strauch, Hua Tang, Kent D. Taylor, Michael Y. Tsai, Jaakko Tuomilehto, André G. Uitterlinden, M. Yldau van der Ende, Diana van Heemst, Trudy Voortman, Mélanie Waldenberger, Patrik Wennberg, Gregory Wilson, Yong-Bing Xiang, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Alan B Zonderman, Diane M Becker, Michael Boehnke, Donald W. Bowden, Ulf dé Fairé, Ian J. Deary, Paul Elliott, Tõnu Esko, Barry I Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Norihiro Kato, Markku Laakso, Timo A Lakka, Terho Lehtimäki, Patrik K. E. Magnusson, Albertine J. Oldehinkel, Brenda W.J.H. Penninx, Nilesh J Samani, Xiao‐Ou Shu, Pim van der Harst, Jana V. van Vliet‐Ostaptchouk, Péter Vollenweider, Lynne E Wagenknecht, Ya X Wang, Nicholas J. Wareham, David R. Weir, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Michele K. Evans, Paul W. Franks, Vilmundur Guðnason, Caroline Hayward, Bernardo Lessa Horta, Tanika N. Kelly, Ching‐Ti Liu, Kari E North, Alexandre C. Pereira, Paul M. Ridker, E Shyong Tai, Rob M. van Dam, Ervin R. Fox, Sharon L.R. Kardia, Ching‐Ti Liu, Dennis O Mook-Kanamori, Michael A. Province, Susan Redline, Cornelia M. van Duijn, Jerome I Rotter, Charles B Kooperberg, W. James Gauderman, Bruce M. Psaty, Kenneth Rice, Patricia B. Munroe, Myriam Fornage, L. Adrienne Cupples, Charles N Rotimi, Alanna C Morrison, D. C. Rao, Ruth J. F. Loos - Nature Communications 2019 被引用: 111

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.