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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

TitleGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.
Publication TypeJournal Article
Year of Publication2017
AuthorsJustice AE, Winkler TW, Feitosa MF, et al.
Secondary AuthorsL Cupples A
JournalNat Commun
Volume8
Pagination14977
Date Published2017 04 26
ISSN2041-1723
KeywordsAdiposity, Adult, Body Fat Distribution, Body Mass Index, Epistasis, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Smoking, Waist Circumference, Waist-Hip Ratio
Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

DOI10.1038/ncomms14977
Alternate JournalNat Commun
PubMed ID28443625
PubMed Central IDPMC5414044
Grant ListHHSN268201200036C / HL / NHLBI NIH HHS / United States
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G1001799 / MRC_ / Medical Research Council / United Kingdom
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