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

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  • Anne E Justice
  • Thomas W Winkler
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  • Virginia A Fisher
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  • Xuan Deng
  • Jacek Czajkowski
  • David Hadley
  • Julius S Ngwa
  • Audrey Y Chu
  • Nancy L Heard-Costa
  • Elise Lim
  • Jeremiah Perez
  • John D Eicher
  • Zoltan Kutalik
  • Luting Xue
  • Anubha Mahajan
  • Frida Renström
  • Joseph C Wu
  • Qibin Qi
  • Shafqat Ahmad
  • Tamuno Alfred
  • Najaf Amin
  • Lawrence F Bielak
  • Amélie Bonnefond
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  • Marie Neergaard Harder
  • Momoko Horikoshi
  • Tao-wei Huang
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  • Ani Manichaikul
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  • Peter J van der Most
  • Jana V van Vliet-Ostaptchouk
  • Sailaja L Vedantam
  • Niek Verweij
  • Jacqueline M Vink
  • Veronique Vitart
  • Ying Wu
  • Loic Yengo
  • Weihua Zhang
  • Jing Hua Zhao
  • Martina E Zimmermann
  • Niha Zubair
  • Goncalo R Abecasis
  • Linda S Adair
  • Saima Afaq
  • Uzma Afzal
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  • Steve Buyske
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  • Joanne E Curran
  • Gert Jan de Borst
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  • George Dedoussis
  • Graciela E Delgado
  • Hester M den Ruijter
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  • Tõnu Esko
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  • Ian Ford
  • Terrence Forrester
  • Karl Gertow
  • Bruna Gigante
  • Nicola Glorioso
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  • Saskia Haitjema
  • Göran Hallmans
  • Anders Hamsten
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  • Catharina A Hartman
  • Maija Hassinen
  • Nicholas D Hastie
  • Andrew C Heath
  • Dena Hernandez
  • Lucia A Hindorff
  • Lynne J Hocking
  • Mette Hollensted
  • Oddgeir L Holmen
  • Georg Homuth
  • Jouke Jan Hottenga
  • Jie Huang
  • Joseph Hung
  • Nina Hutri-Kähönen
  • Erik Ingelsson
  • Alan L James
  • John-Olov Jansson
  • Marjo Riitta Jarvelin
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  • Magnus Karlsson
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  • Cecilia M Lindgren
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  • Marie Loh
  • Mattias Lorentzon
  • Robert Luben
  • Gitta Lubke
  • Anja Ludolph-Donislawski
  • Sara Lupoli
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  • Reija Männikkö
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  • Colin A Mckenzie
  • Barbara McKnight
  • Dan Mellström
  • Cristina Menni
  • Grant W. Montgomery
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  • Matthias Nauck
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  • Albertine J Oldehinkel
  • Matthias Olden
  • Ken K Ong
  • Sandosh Padmanabhan
  • Patricia A Peyser
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  • Kent D Taylor
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  • Gerard Waeber
  • Melanie Waldenberger
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  • Wei Zhao
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  • Damiano Baldassarre
  • Beverley Balkau
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  • Dorret I Boomsma
  • Claude Bouchard
  • Marcel Bruinenberg
  • Daniel I Chasman
  • Yii-DerIda Chen
  • Peter S Chines
  • Richard S Cooper
  • Francesco Cucca
  • Daniele Cusi
  • Ulf de Faire
  • Luigi Ferrucci
  • Paul W Franks
  • Philippe Froguel
  • Penny Gordon-Larsen
  • Hans Jörgen Grabe
  • Vilmundur Gudnason
  • Christopher A Haiman
  • Caroline Hayward
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  • Sharon L R Kardia
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  • Terho Lehtimäki
  • Loic Le Marchand
  • Winfried März
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  • Claes Ohlsson
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  • Rainer Rauramaa
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  • Konstantin Strauch
  • Henning Tiemeier
  • Elena Tremoli
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  • Peter Vollenweider
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  • Jessica Tyrrell
  • Timothy M Frayling
  • Inês Barroso
  • Michael Boehnke
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  • Caroline S Fox
  • Joel N Hirschhorn
  • David J Hunter
  • Tim D Spector
  • David P Strachan
  • Cornélia M van Duijn
  • Iris M Heid
  • Karen L Mohlke
  • Jonathan L Marchini
  • Ruth J F Loos
  • Ching-Ti Liu
  • Ingrid B Borecki
  • Kari E North
  • L Adrienne Cupples

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.

OriginalsprogEngelsk
Artikelnummer14977
TidsskriftNature Communications
Vol/bind8
Antal sider19
ISSN2041-1723
DOI
StatusUdgivet - 26 apr. 2017

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