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

Nat Commun
Authors
Anne Justice
Thomas Winkler
Mary Feitosa
Misa Graff
Virginia Fisher
Kristin Young
Llilda Barata
Xuan Deng
Jacek Czajkowski
David Hadley
Julius Ngwa
Tarunveer Ahluwalia
Audrey Chu
Nancy Heard-Costa
Elise Lim
Jeremiah Perez
John Eicher
Zoltán Kutalik
Luting Xue
Anubha Mahajan
Frida Renström
Joseph Wu
Qibin Qi
Shafqat Ahmad
Tamuno Alfred
Najaf Amin
Lawrence Bielak
Amelie Bonnefond
Jennifer Bragg
Gemma Cadby
Martina Chittani
Scott Coggeshall
Tanguy Corre
Nese Direk
Joel Eriksson
Krista Fischer
Mathias Gorski
Marie Harder
Momoko Horikoshi
Tao Huang
Jennifer Huffman
Anne Jackson
Johanne Justesen
Stavroula Kanoni
Leena Kinnunen
Marcus Kleber
Pirjo Komulainen
Meena Kumari
Unhee Lim
Jian'an Luan
Leo-Pekka Lyytikäinen
Massimo Mangino
Ani Manichaikul
Jonathan Marten
Rita Middelberg
Martina Müller-Nurasyid
Pau Navarro
Louis Pérusse
Natalia Pervjakova
Cinzia Sarti
Albert Smith
Jennifer Smith
Alena Stančáková
Rona Strawbridge
Heather Stringham
Yun Sung
Toshiko Tanaka
Alexander Teumer
Stella Trompet
Sander van der Laan
Peter van der Most
Jana van Vliet-Ostaptchouk
Sailaja Vedantam
Niek Verweij
Jacqueline Vink
Veronique Vitart
Ying Wu
Loic Yengo
Weihua Zhang
Jing Zhao
Martina Zimmermann
Niha Zubair
Gonçalo Abecasis
Linda Adair
Saima Afaq
Uzma Afzal
Stephan Bakker
Traci Bartz
John Beilby
Richard Bergman
Sven Bergmann
Reiner Biffar
John Blangero
Eric Boerwinkle
Lori Bonnycastle
Erwin Bottinger
Daniele Braga
Brendan Buckley
Steve Buyske
Harry Campbell
John Chambers
Francis Collins
Joanne Curran
Gert de Borst
Anton de Craen
Eco De Geus
George Dedoussis
Graciela Delgado
Hester Ruijter
Gudny Eiriksdottir
Anna Eriksson
Tõnu Esko
Jessica Faul
Ian Ford
Terrence Forrester
Karl Gertow
Bruna Gigante
Nicola Glorioso
Jian Gong
Harald Grallert
Tanja Grammer
Niels Grarup
Saskia Haitjema
Göran Hallmans
Anders Hamsten
Torben Hansen
Tamara Harris
Catharina Hartman
Maija Hassinen
Nicholas Hastie
Andrew Heath
Dena Hernandez
Lucia Hindorff
Lynne Hocking
Mette Hollensted
Oddgeir Holmen
Georg Homuth
Jouke Hottenga
Jie Huang
Joseph Hung
Nina Hutri-Kähönen
Erik Ingelsson
Alan James
John-Olov Jansson
Marjo-Riitta Jarvelin
Min Jhun
Marit Jørgensen
Markus Juonala
Mika Kähönen
Magnus Karlsson
Heikki Koistinen
Ivana Kolcic
Genovefa Kolovou
Charles Kooperberg
Bernhard Krämer
Johanna Kuusisto
Kirsti Kvaløy
Timo Lakka
Claudia Langenberg
Lenore Launer
Karin Leander
Nanette Lee
Lars Lind
Cecilia Lindgren
Allan Linneberg
Stéphane Lobbens
Marie Loh
Mattias Lorentzon
Robert Luben
Gitta Lubke
Anja Ludolph-Donislawski
Sara Lupoli
Pamela Madden
Reija Männikkö
Pedro Marques-Vidal
Nicholas Martin
Colin McKenzie
Barbara McKnight
Dan Mellström
Cristina Menni
Grant Montgomery
Aw Musk
Narisu Narisu
Matthias Nauck
Ilja Nolte
Albertine Oldehinkel
Matthias Olden
Ken Ong
Sandosh Padmanabhan
Patricia Peyser
Charlotta Pisinger
David Porteous
Olli Raitakari
Tuomo Rankinen
D Rao
Laura Rasmussen-Torvik
Rajesh Rawal
Treva Rice
Paul Ridker
Lynda Rose
Stephanie Bien
Igor Rudan
Serena Sanna
Mark Sarzynski
Naveed Sattar
Kai Savonen
David Schlessinger
Salome Scholtens
Claudia Schurmann
Robert Scott
Bengt Sennblad
Marten Siemelink
Günther Silbernagel
P Eline Slagboom
Harold Snieder
Jan Staessen
David Stott
Morris Swertz
Amy Swift
Kent Taylor
Bamidele Tayo
Barbara Thorand
Dorothee Thuillier
Jaakko Tuomilehto
André Uitterlinden
Liesbeth Vandenput
Marie-Claude Vohl
Henry Völzke
Judith Vonk
Gérard Waeber
Melanie Waldenberger
R Westendorp
Sarah Wild
Gonneke Willemsen
Bruce Wolffenbuttel
Andrew Wong
Alan Wright
Wei Zhao
M Carola Zillikens
Damiano Baldassarre
Beverley Balkau
Stefania Bandinelli
Carsten Böger
Dorret Boomsma
Claude Bouchard
Marcel Bruinenberg
Daniel Chasman
Yii-DerIda Chen
Peter Chines
Richard Cooper
Francesco Cucca
Daniele Cusi
Ulf de Faire
Luigi Ferrucci
Paul Franks
Philippe Froguel
Penny Gordon-Larsen
Hans-Jörgen Grabe
Vilmundur Gudnason
Christopher Haiman
Caroline Hayward
Kristian Hveem
Andrew Johnson
J Wouter Jukema
Sharon Kardia
Mika Kivimaki
Jaspal Kooner
Diana Kuh
Markku Laakso
Terho Lehtimäki
Loic Le Marchand
Winfried März
Mark McCarthy
Andres Metspalu
Andrew Morris
Claes Ohlsson
Lyle Palmer
Gerard Pasterkamp
Oluf Pedersen
Annette Peters
Ulrike Peters
Ozren Polasek
Bruce Psaty
Lu Qi
Rainer Rauramaa
Blair Smith
Thorkild Sørensen
Konstantin Strauch
Henning Tiemeier
Elena Tremoli
Pim van der Harst
Henrik Vestergaard
Peter Vollenweider
Nicholas Wareham
David Weir
John Whitfield
James Wilson
Jessica Tyrrell
Timothy Frayling
Inês Barroso
Michael Boehnke
Panagiotis Deloukas
Caroline Fox
Joel Hirschhorn
David Hunter
Tim Spector
David Strachan
Cornelia van Duijn
Iris Heid
Karen Mohlke
Jonathan Marchini
Ruth Loos
Tuomas Kilpeläinen
Ching-Ti Liu
Ingrid Borecki
Kari North
L Adrienne Cupples
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.
Year of Publication
2017
Journal
Nat Commun
Volume
8
Pages
14977
Date Published
2017 Apr 26
ISSN
2041-1723
DOI
10.1038/ncomms14977
PubMed ID
28443625
PubMed Central ID
PMC5414044
Links
Grant list
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