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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. Winkler, Thomas W. Feitosa, Mary F. Graff, Misa Fisher, Virginia A. Young, Kristin L. Barata, Llilda Deng, Xuan Czajkowski, Jacek Hadley, David
Justice, Anne E.
Winkler, Thomas W.
Feitosa, Mary F.
Graff, Misa
Fisher, Virginia A.
Young, Kristin L.
Barata, Llilda
Deng, Xuan
Czajkowski, Jacek
Hadley, David
Author
Justice, Anne E.
Winkler, Thomas W.
Feitosa, Mary F.
Graff, Misa
Fisher, Virginia A.
Young, Kristin L.
Barata, Llilda
Deng, Xuan
Czajkowski, Jacek
Hadley, David
Ngwa, Julius S.
Ahluwalia, Tarunveer S.
Chu, Audrey Y.
Heard-Costa, Nancy L.
Lim, Elise
Perez, Jeremiah
Eicher, John D.
Kutalik, Zoltán
Xue, Luting
Mahajan, Anubha
Renström, Frida
Wu, Joseph M. W.
Qi, bin Qi
Ahmad, Shafqat
Alfred, Tamuno
Amin, Najaf
Bielak, Lawrence F.
Bonnefond, Amélie
Bragg, Jennifer L.
Lorentzon, Mattias
Winkler, Thomas W.
Feitosa, Mary F.
Graff, Misa
Fisher, Virginia A.
Young, Kristin L.
Barata, Llilda
Deng, Xuan
Czajkowski, Jacek
Hadley, David
Ngwa, Julius S.
Ahluwalia, Tarunveer S.
Chu, Audrey Y.
Heard-Costa, Nancy L.
Lim, Elise
Perez, Jeremiah
Eicher, John D.
Kutalik, Zoltán
Xue, Luting
Mahajan, Anubha
Renström, Frida
Wu, Joseph M. W.
Qi, bin Qi
Ahmad, Shafqat
Alfred, Tamuno
Amin, Najaf
Bielak, Lawrence F.
Bonnefond, Amélie
Bragg, Jennifer L.
Lorentzon, Mattias
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.
Keywords
Date
2017
Type
Journal article
Journal
Nature Communications
Book
Volume
8
Issue
1
Page Range
1-19
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open
Notes
Please refer to the full article for a complete list of author names.