Accès ouvert déclaré
2024
article
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
J.M. Norris, Εvangelos Εvangelou, C.E. Lewis, André G. Uitterlinden, M.Y. Tsai, N.D. Palmer, Chiamaka Nwuba, S.K. Musani, Xueling Sim, George Papanicolau, Michael R. Brown, S.C. Hunt, Nancy L. Pedersen, Jian‐Min Yuan, R. Dorajoo, J.A. Smith, Marco Brumat, K.L. Mohlke, Morris A. Swertz, Barry I. Freedman, Erin B. Ware, Raymond Noordam, Xiao‐Ou Shu, A. Manning, Olli T. Raitakari, L.-P. Lyytikäinen, S.E. Harris, Rozenn N. Lemaître, Ιωάννα Ντάλλα, Peter J. van der Most, Gregory Wilson, L.J. Launer, Nicola Franceschini, Diane M. Becker, K. Schwander, J.D. Faul, Annette Peters, Christian Gieger, M. Boehnke, Barbara Sternfeld, J.M. Starr, Alan B. Zonderman, B. Kühnel, A. Demirkan, N.J. Samani, F. Giulianini, Yuri Milaneschi, Antonietta Robino, Hugues Aschard, M. Ghanbari, Hermina Jakupović, L.R. Yanek, R. de Mutsert, J.V. Van Vliet-Ostaptchouk, Maria Pina Concas, Chuan Gao, Jingjing Liang, D.I. Chasman, J. Kuusisto, T.M. Bartz, X. Chen, T.A. Lakka, T.B. Harris, Harold Snieder, Mélanie Waldenberger, Thomas Meitinger, Reedik Mägi, Brian E. Cade, E. Boerwinkle, M. Laakso, W.-P. Koh, Pamela J. Schreiner, Amy R. Bentley, Paolo Gasparini, K.D. Taylor, José Eduardo Krieger, H. Wang, K.P. Gabriel, M. Graff, R. Rauramaa, Fang‐Chi Hsu, Sami Heikkinen, J.F. Chai, N. Risch, Archie Campbell, Gerjan Navis, Ani Manichaikul, P. Elliott, Thomas W. Winkler, Hua Tang, J.B. Jonas, Ziyi Wang, Mary F. Feitosa, A.V. Smith, Yechiel Friedlander, J Connell, A. Poveda, Karin Leander, Brenda W.J.H. Penninx, Salman M. Tajuddin, Ulf dé Fairé, Christopher P. Nelson, Raha Pazoki, Ozren Polašek, A.R.V.R. Horimoto, Niek Verweij, Ian J. Deary, Mike A. Nalls, Yongjun Sung, Konstantin Strauch, Jianhua Zhao, A.T. Kraja, Carl D. Langefeld, Zoltán Kutalik, Jie Yao, C.B. Eaton, Jonathan Marten, Stella Aslibekyan, C. Li, H.M. Stringham, Xiuqing Guo, Muhammad Naeem Riaz, David J. Porteous, Miao He, Patrik Wennberg, Pim van der Harst, Jiang He, Caizheng Yu, Yong‐Bing Xiang, T.V. Varga, Bruce H. R. Wolffenbuttel, Patricia A. Peyser, Donald W. Bowden, Claudia Langenberg, J. Ding, F. Takeuchi, Alison D. Murray, Rico Rueedi, L. de las Fuentes, H.J. de Silva, Jeffrey R. O’Connell, Y.-D.I. Chen, Thomas H. Mosley, A. Metspalu, Péter Vollenweider, Mickaël Canouil, Wei Zhao, Behrooz Z. Alizadeh, Cisca Wijmenga, M.A. Ikram, A.U. Jackson, Chao Gu, Kurt K. Lohman, N. Amin, Mario Sims, R.A. Scott, H. Marike Boezen, Lynda M. Rose, Marianne G. Rots, Marzyeh Amini, Patrik K. E. Magnusson, Trudy Voortman, D. Gu, M.Y. van der Ende, Tamar Sofer, S.S. Sidney, Stephen B. Kritchevsky, Jian-Ren Liu, D.K. Arnett, Chew‐Kiat Heng, S.S. Rich, Virginia Fisher, Norihiro Kato, Igor Rudan, Jennifer G. Robinson, F.P. Hartwig, Philippe Froguel, Dina Vojinović, Tõnu Esko, J. Tuomilehto, P. Komulainen, M. Richard, Minjung Kho, T.O. Kilpeläinen, Xiaohui Li, L. Franke, Ilja M. Nolte, Jasmin Divers, Federica Laguzzi, P.S. de Vries, Albertine J. Oldehinkel, Mathilde Boissel, Lawrence F. Bielak, Maris Alver, Terho Lehtimäki
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Résumé fourni par la source
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.
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Genetic Associations and EpidemiologyAdipose Tissue and MetabolismMetabolomics and Mass Spectrometry Studies