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

Kilpelainen, Tuomas O. and Bentley, Amy R. and Noordam, Raymond and Sung, Yun Ju and Schwander, Karen and Winkler, Thomas W. and Jakupovic, Hermina and Chasman, Daniel I. and Manning, Alisa and Ntalla, Ioanna and Aschard, Hugues and Brown, Michael R. and de las Fuentes, Lisa and Franceschini, Nora and Guo, Xiuqing and Vojinovic, Dina and Aslibekyan, Stella and Feitosa, Mary F. and Kho, Minjung and Musani, Solomon K. and Richard, Melissa and Wang, Heming and Wang, Zhe and Bartz, Traci M. and Bielak, Lawrence F. and Campbell, Archie and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P. and Horimoto, Andrea R. V. R. and Li, Changwei and Lohman, Kurt K. and Marten, Jonathan and Sim, Xueling and Smith, Albert V. and Tajuddin, Salman M. and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Graff, Mariaelisa and Harris, Sarah E. and He, Meian and Hsu, Fang-Chi and Jackson, Anne U. and Zhao, Jing Hua and Kraja, Aldi T. and Kuehnel, Brigitte and Laguzzi, Federica and Lyytikainen, Leo-Pekka and Nolte, Ilja M. and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Rueedi, Rico and Stringham, Heather M. and Takeuchi, Fumihiko and van der Most, Peter J. and Varga, Tibor V. and Verweij, Niek and Ware, Erin B. and Wen, Wanqing and Li, Xiaoyin and Yanek, Lisa R. and Amin, Najaf and Arnett, Donna K. and Boerwinkle, Eric and Brumat, Marco and Cade, Brian and Canouil, Mickael and Chen, Yii-Der Ida and Concas, Maria Pina and Connell, John and de Mutsert, Renee and de Silva, H. Janaka and de Vries, Paul S. and Demirkan, Ayse and Ding, Jingzhong and Eaton, Charles B. and Faul, Jessica D. and Friedlander, Yechiel and Gabriel, Kelley P. and Ghanbari, Mohsen and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Harris, Tamara B. and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven C. and Ikram, M. Arfan and Jonas, Jost B. and Koh, Woon-Puay and Komulainen, Pirjo and Krieger, Jose E. and Kritchevsky, Stephen B. and Kutalik, Zoltan and Kuusisto, Johanna and Langefeld, Carl D. and Langenberg, Claudia and Launer, Lenore J. and Leander, Karin and Lemaitre, Rozenn N. and Lewis, Cora E. and Liang, Jingjing and Alizadeh, Behrooz Z. and Boezen, H. Marike and Franke, Lude and Navis, Gerjan and Rots, Marianne and Swertz, Morris and Wolffenbuttel, Bruce H. R. and Wijmenga, Cisca and Liu, Jianjun and Magi, Reedik and Manichaikul, Ani and Meitinger, Thomas and Metspalu, Andres and Milaneschi, Yuri and Mohlke, Karen L. and Mosley, Thomas H. and Murray, Alison D. and Nalls, Mike A. and Nang, Ei-Ei Khaing and Nelson, Christopher P. and Nona, Sotoodehnia and Norris, Jill M. and Nwuba, Chiamaka Vivian and O'Connell, Jeff and Palmer, Nicholette D. and Papanicolau, George J. and Pazoki, Raha and Pedersen, Nancy L. and Peters, Annette and Peyser, Patricia A. and Polasek, Ozren and Porteous, David J. and Poveda, Alaitz and Raitakari, Olli T. and Rich, Stephen S. and Risch, Neil and Robinson, Jennifer G. and Rose, Lynda M. and Rudan, Igor and Schreiner, Pamela J. and Scott, Robert A. and Sidney, Stephen S. and Sims, Mario and Smith, Jennifer A. and Snieder, Harold and Sofer, Tamar and Starr, John M. and Sternfeld, Barbara and Strauch, Konstantin and Tang, Hua and Taylor, Kent D. and Tsai, Michael Y. and Tuomilehto, Jaakko and Uitterlinden, Andre G. and van der Ende, M. Yldau and van Heemst, Diana and Voortman, Trudy and Waldenberger, Melanie and Wennberg, Patrik and Wilson, Gregory and Xiang, Yong-Bing and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Zonderman, Alan B. and Becker, Diane M. and Boehnke, Michael and Bowden, Donald W. and de Faire, Ulf and Deary, Ian J. and Elliott, Paul and Esko, Tonu and Freedman, Barry I. and Froguel, Philippe and Gasparini, Paolo and Gieger, Christian and Kato, Norihiro and Laakso, Markku and Lakka, Timo A. and Lehtimaki, Terho and Magnusson, Patrik K. E. and Oldehinkel, Albertine J. and Penninx, Brenda W. J. H. and Samani, Nilesh J. and Shu, Xiao-Ou and van der Harst, Pim and Van Vliet-Ostaptchouk, Jana V. and Vollenweider, Peter and Wagenknecht, Lynne E. and Wang, Ya X. and Wareham, Nicholas J. and Weir, David R. and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Evans, Michele K. and Franks, Paul W. and Gudnason, Vilmundur and Hayward, Caroline and Horta, Bernardo L. and Kelly, Tanika N. and Liu, Yongmei and North, Kari E. and Pereira, Alexandre C. and Ridker, Paul M. and Tai, E. Shyong and van Dam, Rob M. and Fox, Ervin R. and Kardia, Sharon L. R. and Liu, Ching-Ti and Mook-Kanamori, Dennis O. and Province, Michael A. and Redline, Susan and van Duijn, Cornelia M. and Rotter, Jerome I. and Kooperberg, Charles B. and Gauderman, W. James and Psaty, Bruce M. and Rice, Kenneth and Munroe, Patricia B. and Fornage, Myriam and Cupples, L. Adrienne and Rotimi, Charles N. and Morrison, Alanna C. and Rao, Dabeeru C. and Loos, Ruth J. F. (2019) Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. NATURE COMMUNICATIONS, 10: 376. ISSN 2041-1723,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: WIDE ASSOCIATION; METAANALYSIS; INDIVIDUALS; CARBOXYLASE; EXERCISE; REVEAL; SNP;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 27 Apr 2020 07:02
Last Modified: 27 Apr 2020 07:02
URI: https://pred.uni-regensburg.de/id/eprint/27711

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