@article {12128, title = {Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.}, journal = {Nature Communications}, volume = {10}, year = {2019}, pages = {376}, 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.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Asians, Blacks, Brazil, Calcium-Binding Proteins, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Exercise, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, LIM-Homeodomain Proteins, Lipid Metabolism, Lipids, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Muscle Proteins, Nerve Tissue Proteins, Transcription Factors, Triglycerides, Whites, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-08008-w}, author = {Kilpel{\"a}inen, Tuomas O and Bentley, Amy R and Noordam, Raymond and Yun Ju Sung and Schwander, Karen and Thomas W Winkler and Jakupovi{\'c}, Hermina and Daniel I Chasman and Alisa Manning 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 Melissa Richard and Wang, Heming and Wang, Zhe and Traci M Bartz 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 Kurt Lohman and Marten, Jonathan and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Jin-Fang Chai and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Graff, Mariaelisa and Sarah E Harris and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and Jing Hua Zhao and Kraja, Aldi T and K{\"u}hnel, Brigitte and Laguzzi, Federica and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Rueedi, Rico and Heather M Stringham and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Verweij, Niek and Erin B Ware and Wen, Wanqing and Li, Xiaoyin and Yanek, Lisa R and Amin, Najaf and Donna K Arnett and Boerwinkle, Eric and Brumat, Marco and Brian E Cade and Canouil, Micka{\"e}l and Chen, Yii-Der Ida and Concas, Maria Pina and Connell, John and de Mutsert, Ren{\'e}e and de Silva, H Janaka and de Vries, Paul S and Demirkan, Ayse and Ding, Jingzhong and Charles B Eaton and Jessica Faul and Friedlander, Yechiel and Gabriel, Kelley P and Ghanbari, Mohsen and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Tamara B Harris and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven C and Ikram, M Arfan and Jost Bruno Jonas and Koh, Woon-Puay and Komulainen, Pirjo and Krieger, Jose E and Stephen B Kritchevsky and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Lenore J Launer and Leander, Karin and Lemaitre, Rozenn N and Lewis, Cora E and Liang, Jingjing and Liu, Jianjun and M{\"a}gi, Reedik and Manichaikul, Ani and Meitinger, Thomas and Andres Metspalu and Milaneschi, Yuri and Mohlke, Karen L and Thomas H Mosley and Murray, Alison D and Michael A Nalls and Nang, Ei-Ei Khaing and Nelson, Christopher P and Nona, Sotoodehnia and Norris, Jill M and Nwuba, Chiamaka Vivian and Jeff O{\textquoteright}Connell and Palmer, Nicholette D and Papanicolau, George J and Pazoki, Raha and Nancy L Pedersen and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and David J Porteous and Poveda, Alaitz and Olli T Raitakari and Rich, Stephen S and Neil Risch and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Schreiner, Pamela J and Scott, Robert A and Stephen Sidney and Sims, Mario and Smith, Jennifer A and Snieder, Harold and Sofer, Tamar and John M Starr and Sternfeld, Barbara and Strauch, Konstantin and Tang, Hua and Kent D Taylor and Tsai, Michael Y and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden 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 Alan B Zonderman and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and de Faire, Ulf and Ian J Deary and Elliott, Paul and T{\~o}nu Esko and Freedman, Barry I and Froguel, Philippe and Paolo P. Gasparini and Gieger, Christian and Kato, Norihiro and Laakso, Markku and Lakka, Timo A and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Oldehinkel, Albertine J and Brenda W J H Penninx and Nilesh J Samani and Shu, Xiao-Ou and van der Harst, Pim and Jana V. van Vliet-Ostaptchouk and Vollenweider, Peter and Wagenknecht, Lynne E and Wang, Ya X and Wareham, Nicholas J and David R Weir and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Michele K Evans and Franks, Paul W and Gudnason, Vilmundur and Caroline Hayward and Horta, Bernardo L and Tanika N Kelly and Liu, Yongmei and Kari E North and Pereira, Alexandre C and Ridker, Paul M and Tai, E Shyong and van Dam, Rob M and Fox, Ervin R and Sharon L R Kardia and Liu, Ching-Ti and Dennis O Mook-Kanamori and Province, Michael A and Redline, Susan and Cornelia M van Duijn and Rotter, Jerome I and Charles Kooperberg and Gauderman, W James and Psaty, Bruce M and Kenneth Rice and Munroe, Patricia B and Myriam Fornage and Cupples, L Adrienne and Charles N Rotimi and Alanna C Morrison and Rao, Dabeeru C and Ruth J F Loos} }