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

Tuomas O Kilpeläinen; Amy R Bentley; Raymond Noordam; Yun Ju Sung; Sarah Harris; Karen Schwander; David Porteous; John Starr; Ian Deary

doi:10.1038/s41467- 018-08008-w

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

Tuomas O Kilpeläinen, Amy R Bentley, Raymond Noordam, Yun Ju Sung, Sarah Harris, Karen Schwander, David Porteous, John Starr, Ian Deary

Research output: Contribution to journal › Article › peer-review

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as 296 physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we 297 performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up 298 to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of 299 suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, 300 and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher 301 levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci 302 and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 303 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical 304 activity interactions in the genetic contribution to blood lipid levels.

Original language	English
Article number	376
Pages (from-to)	1-11
Journal	Nature Communications
DOIs	https://doi.org/10.1038/s41467- 018-08008-w
Publication status	Published - 22 Jan 2019

Keywords / Materials (for Non-textual outputs)

cardiovascular genetics
dyslpidaemias
genome-wide association study

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10.1038/s41467- 018-08008-wLicence: Creative Commons: Attribution (CC-BY)

KilpeläinenEtalNC2018MultiAncestryStudyFinal published version, 1.71 MBLicence: Creative Commons: Attribution (CC-BY)

https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-018-08008-w/MediaObjects/41467_2018_8008_MOESM1_ESM.pdf

The Disconnected Mind Phase 3
Wardlaw, J. (Principal Investigator)
UK-based charities
1/04/16 → 30/09/20
Project: Research
Stratifying Resilience and Depression Longitudinally
McIntosh, A. (Principal Investigator), Deary, I. (Co-investigator), Evans, K. (Co-investigator), Haley, C. (Co-investigator) & Porteous, D. (Co-investigator)
UK-based charities
1/01/15 → 30/06/21
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research

Cite this

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title = "Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity",

abstract = "Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as 296 physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we 297 performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up 298 to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of 299 suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, 300 and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher 301 levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci 302 and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 303 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical 304 activity interactions in the genetic contribution to blood lipid levels. ",

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doi = "10.1038/s41467- 018-08008-w",

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AU - Kilpeläinen, Tuomas O

AU - Bentley, Amy R

AU - Noordam, Raymond

AU - Ju Sung, Yun

AU - Harris, Sarah

AU - Schwander, Karen

AU - Porteous, David

AU - Starr, John

AU - Deary, Ian

N1 - Published Gold

PY - 2019/1/22

Y1 - 2019/1/22

N2 - Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as 296 physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we 297 performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up 298 to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of 299 suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, 300 and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher 301 levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci 302 and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 303 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical 304 activity interactions in the genetic contribution to blood lipid levels.

AB - Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as 296 physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we 297 performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up 298 to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of 299 suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, 300 and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher 301 levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci 302 and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 303 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical 304 activity interactions in the genetic contribution to blood lipid levels.

KW - cardiovascular genetics

KW - dyslpidaemias

KW - genome-wide association study

U2 - 10.1038/s41467- 018-08008-w

DO - 10.1038/s41467- 018-08008-w

M3 - Article

SN - 2041-1723

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

M1 - 376

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

The Disconnected Mind Phase 3

Stratifying Resilience and Depression Longitudinally

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

Cite this