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

Kilpeläinen, Tuomas O ; V. Varga, Tibor LU ; Poveda, Alaitz LU orcid ; Franks, Paul LU ; Rao, Dabeeru C. and Loos, Ruth J. F. (2019) In Nature Communications 10(1).
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,... (More)
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. © 2019, The Author(s). (Less)
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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
10
issue
1
article number
376
publisher
Nature Publishing Group
external identifiers
  • pmid:30670697
  • scopus:85060388984
ISSN
2041-1723
DOI
10.1038/s41467-018-08008-w
language
English
LU publication?
yes
additional info
Export Date: 1 February 2019
id
ddccdd28-505a-425f-bbb9-5250d5206f47
date added to LUP
2019-02-01 08:28:35
date last changed
2022-04-25 20:38:50
@article{ddccdd28-505a-425f-bbb9-5250d5206f47,
  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. © 2019, The Author(s).}},
  author       = {{Kilpeläinen, Tuomas O and V. Varga, Tibor and Poveda, Alaitz and Franks, Paul and Rao, Dabeeru C. and Loos, Ruth J. F.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity}},
  url          = {{http://dx.doi.org/10.1038/s41467-018-08008-w}},
  doi          = {{10.1038/s41467-018-08008-w}},
  volume       = {{10}},
  year         = {{2019}},
}