Title | Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Kilpeläinen TO, Bentley AR, Noordam R, et al. |
Secondary Authors | Loos RJF |
Corporate Authors | LifeLines Cohort Study |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 376 |
Date Published | 2019 01 22 |
ISSN | 2041-1723 |
Keywords | Adolescent, 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. |
DOI | 10.1038/s41467-018-08008-w |
Alternate Journal | Nat Commun |
PubMed ID | 30670697 |
PubMed Central ID | PMC6342931 |
Grant List | R01 DK072193 / DK / NIDDK NIH HHS / United States MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom R01 AG055406 / AG / NIA NIH HHS / United States MR/R023484/1 / MRC_ / Medical Research Council / United Kingdom P30 DK020572 / DK / NIDDK NIH HHS / United States BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom P2C HD050924 / HD / NICHD NIH HHS / United States K01 HL135405 / HL / NHLBI NIH HHS / United States R01 DK093757 / DK / NIDDK NIH HHS / United States MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom U01 HG007417 / HG / NHGRI NIH HHS / United States K01 HL136700 / HL / NHLBI NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States MR/L01632X/1 / MRC_ / Medical Research Council / United Kingdom R01 HL142302 / HL / NHLBI NIH HHS / United States R01 DK107786 / DK / NIDDK NIH HHS / United States P30 DK079626 / DK / NIDDK NIH HHS / United States P30 DK056341 / DK / NIDDK NIH HHS / United States R01 DK075787 / DK / NIDDK NIH HHS / United States MR/L01341X/1 / MRC_ / Medical Research Council / United Kingdom MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom R01 HL119443 / HL / NHLBI NIH HHS / United States R01 HL118305 / HL / NHLBI NIH HHS / United States R01 DK062370 / DK / NIDDK NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 DK062370 / DK / NIDDK NIH HHS / United States M01 RR000032 / RR / NCRR NIH HHS / United States T32 DK091317 / DK / NIDDK NIH HHS / United States P01 CA196569 / CA / NCI NIH HHS / United States |