Multi-ancestry genome-wide smoking interaction study of 387,272 individuals identifies novel lipid loci.

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Title: Multi-ancestry genome-wide smoking interaction study of 387,272 individuals identifies novel lipid loci.
Authors: Bentley, AR
Evangelou, E
Zhang, W
Afaq, S
Lehne, B
Poulter, N
Sever, P
Chambers, J
Elliott, P
Froguel, P
Scott, J
Cupples, A
Item Type: Journal Article
Abstract: Serum lipids, such as triglycerides (TG) and high- and low-density lipoprotein cholesterol (HDL and LDL), are influenced by both genetic and lifestyle factors. Over 250 lipid loci have been identified,1-6 yet, it is unclear to what extent lifestyle factors modify the effects of these variants, or those yet to be identified. Smoking is associated with an unfavorable lipid profile,7,8 warranting its investigation as a lifestyle factor that potentially modifies genetic associations with lipids. Identifying interactions using traditional 1 degree of freedom (1df) tests of SNP x smoking terms may have low power, except in very large sample sizes. To enhance the detection of loci, a 2 degree of freedom (2df) test that jointly evaluates the interaction and main effects was developed.9 The Gene-Lifestyle Interactions Working Group, under the aegis of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium10, was formed to conduct analyses of lifestyle interactions in the genetic basis of cardiovascular traits. As both genetic and lifestyle factors differ across populations with different ancestry backgrounds, and to address the underrepresentation of non-European populations in genomic research, great effort went into creating a large, multi-ancestry resource for these investigations.11 Here, we report a genome-wide interaction study that uses both the 1df test of interaction and the 2df joint test of main and interaction effects to test the hypothesis that genetic associations of serum lipids differ by smoking status.
Date of Acceptance: 29-Nov-2018
URI: http://hdl.handle.net/10044/1/66600
ISSN: 1061-4036
Publisher: Nature Research
Journal / Book Title: Nature Genetics
Sponsor/Funder: Home Office
Medical Research Council (MRC)
Action on Hearing Loss
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: PG0484
G0601966
G51_Chambers
MR/L01632X/1
MR/L01632X/1
MR/L01341X/1
RDF03
Keywords: 11 Medical And Health Sciences
06 Biological Sciences
Developmental Biology
Publication Status: Accepted
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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