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

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Authors

  • Anne E. Justice
  • Thomas W. Winkler
  • Mary F. Feitosa
  • Misa Graff
  • Virginia A. Fisher
  • Kristin Young
  • And 311 others
  • Llilda Barata
  • Xuan Deng
  • Jacek Czajkowski
  • David Hadley
  • Julius S. Ngwa
  • Tarunveer S. Ahluwalia
  • Audrey Y. Chu
  • Nancy L. Heard-Costa
  • Elise Lim
  • Jeremiah Perez
  • John D. Eicher
  • Zolta'n Kutalik
  • Luting Xue
  • Anubha Mahajan
  • Frida Renström
  • Joseph Wu
  • Qibin Qi
  • Shafqat Ahmad
  • Tamuno Alfred
  • Najaf Amin
  • Lawrence F. Bielak
  • Amelie Bonnefond
  • Jennifer Bragg
  • Gemma Cadby
  • Martina Chittani
  • Scott Coggeshall
  • Tanguy Corre
  • Nese Direk
  • Joel Eriksson
  • Krista Fischer
  • Mathias Gorski
  • Marie Neergaard Harder
  • Momoko Horikoshi
  • Tao Huang
  • Jennifer E. Huffman
  • Anne U. Jackson
  • Johanne Marie Justesen
  • Stavroula Kanoni
  • Leena Kinnunen
  • Marcus E. Kleber
  • Pirjo Komulainen
  • Meena Kumari
  • Unhee Lim
  • Jian'an Luan
  • Leo Pekka Lyytikäinen
  • Massimo Mangino
  • Ani Manichaikul
  • Jonathan Marten
  • Rita P.S. Middelberg
  • Martina Müller-Nurasyid
  • Pau Navarro
  • Louis Pe'russe
  • Natalia Pervjakova
  • Cinzia Sarti
  • Albert Vernon Smith
  • Jennifer A. Smith
  • Alena Stanča'kova
  • Rona J. Strawbridge
  • Heather M. Stringham
  • Yun Ju Sung
  • Toshiko Tanaka
  • Alexander Teumer
  • Stella Trompet
  • Sander W. Van Der Laan
  • 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
  • Gonçalo R. Abecasis
  • Linda S. Adair
  • Saima Afaq
  • Uzma Afzal
  • Stephan J.L. Bakker
  • Traci M. Bartz
  • John Beilby
  • Richard N. Bergman
  • Sven Bergmann
  • Reiner Biffar
  • John Blangero
  • Eric Boerwinkle
  • Lori L. Bonnycastle
  • Erwin Bottinger
  • Daniele Braga
  • Brendan M. Buckley
  • Steve Buyske
  • Harry Campbell
  • John C. Chambers
  • Francis S. Collins
  • Joanne E. Curran
  • Gert J. De Borst
  • Anton J.M. De Craen
  • Eco J.C. De Geus
  • George Dedoussis
  • Graciela E. Delgado
  • Hester M. Den Ruijter
  • Gudny Eiriksdottir
  • Anna L. Eriksson
  • Toñu Esko
  • Jessica D. Faul
  • Ian Ford
  • Terrence Forrester
  • Karl Gertow
  • Bruna Gigante
  • Nicola Glorioso
  • Jian Gong
  • Harald Grallert
  • Tanja B. Grammer
  • Niels Grarup
  • Saskia Haitjema
  • Göran Hallmans
  • Anders Hamsten
  • Torben Hansen
  • Tamara B. Harris
  • Catharina A. Hartman
  • Maija Hassinen
  • Nicholas D. Hastie
  • Andrew C. Heath
  • Dena Hernandez
  • Lucia 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
  • Min A. Jhun
  • Marit E. Jorgensen
  • Markus Juonala
  • Mika Kähönen
  • Magnus Karlsson
  • Heikki A. Koistinen
  • Ivana Kolcic
  • Genovefa Kolovou
  • Charles Kooperberg
  • Bernhard K. Krämer
  • Johanna Kuusisto
  • Kirsti Kvaloy
  • Timo A. Lakka
  • Claudia Langenberg
  • Lenore J. Launer
  • Karin Leander
  • Nanette R. Lee
  • Lars Lind
  • Cecilia M. Lindgren
  • Allan Linneberg
  • Stephane Lobbens
  • Marie Loh
  • Mattias Lorentzon
  • Robert Luben
  • Gitta Lubke
  • Anja Ludolph-Donislawski
  • Sara Lupoli
  • Pamela A.F. Madden
  • Reija Männikkö
  • Pedro Marques-Vidal
  • Nicholas G. Martin
  • Colin A. McKenzie
  • Barbara McKnight
  • Dan Mellström
  • Cristina Menni
  • Grant W. Montgomery
  • A. W. Musk
  • Narisu Narisu
  • Matthias Nauck
  • Ilja M. Nolte
  • Albertine J. Oldehinkel
  • Matthias Olden
  • Ken K. Ong
  • Sandosh Padmanabhan
  • Patricia A. Peyser
  • Charlotta Pisinger
  • David J. Porteous
  • Olli T. Raitakari
  • Tuomo Rankinen
  • D. C. Rao
  • Laura J. Rasmussen-Torvik
  • Rajesh Rawal
  • Treva Rice
  • Paul M. Ridker
  • Lynda M. Rose
  • Stephanie A. Bien
  • Igor Rudan
  • Serena Sanna
  • Mark A. Sarzynski
  • Naveed Sattar
  • Kai Savonen
  • David Schlessinger
  • Salome Scholtens
  • Claudia Schurmann
  • Robert A. Scott
  • Bengt Sennblad
  • Marten A. Siemelink
  • Günther Silbernagel
  • P. Eline Slagboom
  • Harold Snieder
  • Jan A. Staessen
  • David J. Stott
  • Morris A. Swertz
  • Amy J. Swift
  • Kent D. Taylor
  • Bamidele O. Tayo
  • Barbara Thorand
  • Dorothee Thuillier
  • Jaakko Tuomilehto
  • Andre G. Uitterlinden
  • Liesbeth Vandenput
  • Marie Claude Vohl
  • Henry Völzke
  • Judith M. Vonk
  • Ge'rard Waeber
  • Melanie Waldenberger
  • R. G.J. Westendorp
  • Sarah Wild
  • Gonneke Willemsen
  • Bruce H.R. Wolffenbuttel
  • Andrew Wong
  • Alan F. Wright
  • Wei Zhao
  • M. Carola Zillikens
  • Damiano Baldassarre
  • Beverley Balkau
  • Stefania Bandinelli
  • Carsten A. Böger
  • Dorret I. Boomsma
  • Claude Bouchard
  • Marcel Bruinenberg
  • Daniel I. Chasman
  • Yii Der Ida 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
  • Kristian Hveem
  • Andrew D. Johnson
  • J. Wouter Jukema
  • Sharon L.R. Kardia
  • Mika Kivimaki
  • Jaspal S. Kooner
  • Diana Kuh
  • Markku Laakso
  • Terho Lehtimäki
  • Loic Le Marchand
  • Winfried März
  • Mark I. McCarthy
  • Andres Metspalu
  • Andrew P. Morris
  • Claes Ohlsson
  • Lyle J. Palmer
  • Gerard Pasterkamp
  • Oluf Pedersen
  • Annette Peters
  • Ulrike Peters
  • Ozren Polasek
  • Bruce M. Psaty
  • Lu Qi
  • Rainer Rauramaa
  • Blair H. Smith
  • Thorkild I.A. Sorensen
  • Konstantin Strauch
  • Henning Tiemeier
  • Elena Tremoli
  • Pim Van Der Harst
  • Henrik Vestergaard
  • Peter Vollenweider
  • Nicholas J. Wareham
  • David R. Weir
  • John B. Whitfield
  • James F. Wilson
  • Jessica Tyrrell
  • Timothy M. Frayling
  • Inês Barroso
  • Michael Boehnke
  • Panagiotis Deloukas
  • Caroline S. Fox
  • Joel N. Hirschhorn
  • David J. Hunter
  • Tim D. Spector
  • David P. Strachan
  • Cornelia M. Van Duijn
  • Iris M. Heid
  • Karen L. Mohlke
  • Jonathan Marchini
  • Ruth J.F. Loos
  • Tuomas O. Kilpeläinen
  • Ching Ti Liu
  • Ingrid B. Borecki
  • Kari E. North
  • L. Adrienne Cupples

Research units

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.

Peer-reviewedYes
Original languageEnglish
Article number14977
JournalNature Communications
Volume8
DOIs
StatePublished - 26 Apr 2017


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