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

Research output: Contribution to journalArticle

Authors

  • Lifelines Cohort Study

External Institution(s)

  • University of Copenhagen
  • Icahn School of Medicine at Mount Sinai
  • National Institutes of Health
  • Leiden University
  • Washington University St. Louis
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  • German Center for Diabetes Research (DZD e.V.)
  • Interuniversity Cardiology Institute of the Netherlands
  • University of Oxford
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  • University of Southern California

Details

Original languageEnglish (US)
Article number376
JournalNature communications
Volume10
Issue number1
StatusPublished - Dec 1 2019
Peer-reviewedYes

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.