Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activityKilpelainen, T. O., Nolte, I. M., van der Most, P. J., Verweij, N., Snieder, H., van der Ende, M. Y., Oldehinkel, A. J., van der Harst, P., Van Vliet-Ostaptchouk, J. V., Lifelines Cohort Study & Wang, Y. X., 22-Jan-2019, In : Nature Communications. 10, 1, 11 p., 376.
Research output: Contribution to journal › Article › Academic › peer-review
- Life Course Epidemiology (LCE)
- Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Groningen Research Institute for Asthma and COPD (GRIAC)
- Lifestyle Medicine (LM)
- Groningen Kidney Center (GKC)
- Value, Affordability and Sustainability (VALUE)
- Damage and Repair in Cancer Development and Cancer Treatment (DARE)
- Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
- Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)
- Cardiovascular Centre (CVC)
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.
|Number of pages||11|
|Publication status||Published - 22-Jan-2019|
- WIDE ASSOCIATION, METAANALYSIS, INDIVIDUALS, CARBOXYLASE, EXERCISE, REVEAL, SNP