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



Justice, Anne E, Winkler, Thomas W, Feitosa, Mary F, Graff, Misa, Fisher, Virginia A, Young, Kristin, Barata, Llilda, Deng, Xuan, Czajkowski, Jacek, Hadley, David
et al (show 307 more authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. NATURE COMMUNICATIONS, 8 (1). 14977-.

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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.

Item Type: Article
Uncontrolled Keywords: Humans, Obesity, Genetic Predisposition to Disease, Body Mass Index, Waist-Hip Ratio, Smoking, Epistasis, Genetic, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Adult, Adiposity, Body Fat Distribution, Waist Circumference, Genome-Wide Association Study
Depositing User: Symplectic Admin
Date Deposited: 02 May 2017 06:35
Last Modified: 16 Dec 2022 01:36
DOI: 10.1038/ncomms14977
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3007177