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

TitleMulti-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Publication TypeJournal Article
Year of Publication2019
AuthorsKilpeläinen, TO, Bentley, AR, Noordam, R, Sung, YJu, Schwander, K, Winkler, TW, Jakupović, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, Fuentes, Lde Las, Franceschini, N, Guo, X, Vojinovic, D, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, H, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, ARVR, Li, C, Lohman, KK, Marten, J, Sim, X, Smith, AV, Tajuddin, SM, Alver, M, Amini, M, Boissel, M, Chai, JFang, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, M, Hsu, F-C, Jackson, AU, Zhao, JHua, Kraja, AT, Kühnel, B, Laguzzi, F, Lyytikäinen, L-P, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, W, Li, X, Yanek, LR, Amin, N, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, Y-DIda, Concas, MPina, Connell, J, de Mutsert, R, H de Silva, J, de Vries, PS, Demirkan, A, Ding, J, Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, M, Giulianini, F, Gu, CCharles, Gu, D, Harris, TB, He, J, Heikkinen, S, Heng, C-K, Hunt, SC, M Ikram, A, Jonas, JB, Koh, W-P, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, J, Liu, J, Mägi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, E-EKhaing, Nelson, CP, Nona, S, Norris, JM, Nwuba, CVivian, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, AG, M van der Ende, Y, van Heemst, D, Voortman, T, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, Y-B, Yao, J, Yu, C, Yuan, J-M, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimäki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, BWJH, Samani, NJ, Shu, X-O, van der Harst, P, Van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, T, Zheng, W, Zhu, X, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, Y, North, KE, Pereira, AC, Ridker, PM, E Tai, S, van Dam, RM, Fox, ER, Kardia, SLR, Liu, C-T, Mook-Kanamori, DO, Province, MA, Redline, S, van Duijn, CM, Rotter, JI, Kooperberg, CB, W Gauderman, J, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, L Cupples, A, Rotimi, CN, Morrison, AC, Rao, DC, Loos, RJF
Corporate AuthorsLifeLines Cohort Study
JournalNat Commun
Volume10
Issue1
Pagination376
Date Published2019 01 22
ISSN2041-1723
KeywordsAdolescent, Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Asian Continental Ancestry Group, Brazil, Calcium-Binding Proteins, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Exercise, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Hispanic Americans, Humans, LIM-Homeodomain Proteins, Lipid Metabolism, Lipids, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Muscle Proteins, Nerve Tissue Proteins, Transcription Factors, Triglycerides, Young Adult
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.

DOI10.1038/s41467-018-08008-w
Alternate JournalNat Commun
PubMed ID30670697
PubMed Central IDPMC6342931
Grant ListK01 HL136700 / HL / NHLBI NIH HHS / United States
MR/L01632X/1 / / Medical Research Council / United Kingdom
R01 HL142302 / HL / NHLBI NIH HHS / United States
P30 DK079626 / DK / NIDDK NIH HHS / United States
MR/L01341X/1 / / Medical Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL118305 / HL / NHLBI NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
P01 CA196569 / CA / NCI NIH HHS / United States