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

Justice, Anne E. ; Renström, Frida LU ; Ahmad, Shafqat LU ; Karlsson, Magnus LU ; Franks, Paul W. LU and Cupples, L Adrienne (2017) In Nature Communications 8.
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... (More)

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.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
8
article number
14977
publisher
Nature Publishing Group
external identifiers
  • scopus:85019322396
  • pmid:28443625
ISSN
2041-1723
DOI
10.1038/ncomms14977
language
English
LU publication?
yes
id
3ab1cab0-3d12-4cb5-b4ff-6eecd0aa3011
date added to LUP
2019-05-21 19:43:22
date last changed
2024-04-16 07:09:04
@article{3ab1cab0-3d12-4cb5-b4ff-6eecd0aa3011,
  abstract     = {{<p>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.</p>}},
  author       = {{Justice, Anne E. and Renström, Frida and Ahmad, Shafqat and Karlsson, Magnus and Franks, Paul W. and Cupples, L Adrienne}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits}},
  url          = {{http://dx.doi.org/10.1038/ncomms14977}},
  doi          = {{10.1038/ncomms14977}},
  volume       = {{8}},
  year         = {{2017}},
}