Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

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  • Mariaelisa Graff
  • Robert A. Scott
  • Anne E. Justice
  • Kristin L. Young
  • Mary F. Feitosa
  • Llilda Barata
  • And 278 others
  • Thomas W. Winkler
  • Audrey Y. Chu
  • Anubha Mahajan
  • David Hadley
  • Luting Xue
  • Tsegaselassie Workalemahu
  • Nancy L. Heard-Costa
  • Marcel den Hoed
  • Tarunveer S. Ahluwalia
  • Qibin Qi
  • Julius S. Ngwa
  • Frida Renström
  • Lydia Quaye
  • John D. Eicher
  • James E. Hayes
  • Marilyn Cornelis
  • Zoltan Kutalik
  • Elise Lim
  • Jian’an Luan
  • Jennifer E. Huffman
  • Weihua Zhang
  • Wei Zhao
  • Paula J. Griffin
  • Toomas Haller
  • Shafqat Ahmad
  • Pedro M. Marques-Vidal
  • Stephanie Bien
  • Loic Yengo
  • Alexander Teumer
  • Albert Vernon Smith
  • Meena Kumari
  • Marie Neergaard Harder
  • Johanne Marie Justesen
  • Marcus E. Kleber
  • Mette Hollensted
  • Kurt Lohman
  • Natalia V. Rivera
  • John B. Whitfield
  • Jing Hua Zhao
  • Heather M. Stringham
  • Leo Pekka Lyytikäinen
  • Charlotte Huppertz
  • Gonneke Willemsen
  • Wouter J. Peyrot
  • Ying Wu
  • Kati Kristiansson
  • Ayse Demirkan
  • Myriam Fornage
  • Maija Hassinen
  • Lawrence F. Bielak
  • Gemma Cadby
  • Toshiko Tanaka
  • Reedik Mägi
  • Peter J. Van Der Most
  • Anne U. Jackson
  • Jennifer L. Bragg-Gresham
  • Veronique Vitart
  • Jonathan Marten
  • Pau Navarro
  • Claire Bellis
  • Dorota Pasko
  • Åsa Johansson
  • Søren Snitker
  • Ching Yu Cheng
  • Joel Eriksson
  • Unhee Lim
  • Mette Aadahl
  • Linda S. Adair
  • Najaf Amin
  • Beverley Balkau
  • Juha Auvinen
  • John Beilby
  • Richard N. Bergman
  • Sven Bergmann
  • Alain G. Bertoni
  • John Blangero
  • Amélie Bonnefond
  • Lori L. Bonnycastle
  • Judith B. Borja
  • Søren Brage
  • Fabio Busonero
  • Steve Buyske
  • Harry Campbell
  • Peter S. Chines
  • Francis S. Collins
  • Tanguy Corre
  • George Davey Smith
  • Graciela E. Delgado
  • Nicole Dueker
  • Marcus Dörr
  • Tapani Ebeling
  • Gudny Eiriksdottir
  • Tõnu Esko
  • Jessica D. Faul
  • Mao Fu
  • Kristine Færch
  • Christian Gieger
  • Sven Gläser
  • Jian Gong
  • Penny Gordon-Larsen
  • Harald Grallert
  • Tanja B. Grammer
  • Niels Grarup
  • Gerard van Grootheest
  • Kennet Harald
  • Nicholas D. Hastie
  • Aki S. Havulinna
  • Dena G. Hernandez
  • Lucia Hindorff
  • Lynne J. Hocking
  • Oddgeir L. Holmens
  • Christina Holzapfel
  • Jouke Jan Hottenga
  • Jie Huang
  • Tao Huang
  • Jennie Hui
  • Cornelia Huth
  • Nina Hutri-Kähönen
  • Alan L. James
  • John Olov Jansson
  • Min A. Jhun
  • Markus Juonala
  • Leena Kinnunen
  • Heikki A. Koistinen
  • Ivana Kolcic
  • Pirjo Komulainen
  • Johanna Kuusisto
  • Kirsti Kvaløy
  • Mika Kähönen
  • Timo A. Lakka
  • Lenore J. Launer
  • Benjamin Lehne
  • Cecilia M. Lindgren
  • Mattias Lorentzon
  • Robert N Luben
  • Michel Marre
  • Yuri Milaneschi
  • Keri L. Monda
  • Grant W. Montgomery
  • Marleen H.M. De Moor
  • Antonella Mulas
  • Martina Müller-Nurasyid
  • A. W. Musk
  • Reija Männikkö
  • Satu Männistö
  • Narisu Narisu
  • Matthias Nauck
  • Jennifer A. Nettleton
  • Ilja M. Nolte
  • Albertine J. Oldehinkel
  • Matthias Olden
  • Ken K. Ong
  • Sandosh Padmanabhan
  • Lavinia Paternoster
  • Jeremiah Perez
  • Markus Perola
  • Annette Peters
  • Ulrike Peters
  • Patricia A. Peyser
  • Inga Prokopenko
  • Hannu Puolijoki
  • Olli T. Raitakari
  • Tuomo Rankinen
  • Laura J. Rasmussen-Torvik
  • Rajesh Rawal
  • Paul M. Ridker
  • Lynda M. Rose
  • Igor Rudan
  • Cinzia Sarti
  • Mark A. Sarzynski
  • Kai Savonen
  • William R. Scott
  • Serena Sanna
  • Alan R. Shuldiner
  • Steve Sidney
  • Günther Silbernagel
  • Blair H. Smith
  • Jennifer A. Smith
  • Harold Snieder
  • Alena Stančáková
  • Barbara Sternfeld
  • Amy J. Swift
  • Tuija Tammelin
  • Sian Tsung Tan
  • Barbara Thorand
  • Dorothée Thuillier
  • Liesbeth Vandenput
  • Henrik Vestergaard
  • Jana V. Van Vliet-Ostaptchouk
  • Marie Claude Vohl
  • Uwe Völker
  • Gérard Waeber
  • Mark Walker
  • Sarah H. Wild
  • Andrew Wong
  • Alan F. Wright
  • M. Carola Zillikens
  • Niha Zubair
  • Christopher A. Haiman
  • Loic Lemarchand
  • Ulf Gyllensten
  • Claes Ohlsson
  • Albert Hofman
  • Fernando Rivadeneira
  • André G. Uitterlinden
  • Louis Pérusse
  • James F. Wilson
  • Caroline Hayward
  • Ozren Polasek
  • Francesco Cucca
  • Kristian Hveem
  • Catharina A. Hartman
  • Anke Tönjes
  • Stefania Bandinelli
  • Lyle J. Palmer
  • Sharon L R Kardia
  • Rainer Rauramaa
  • Thorkild I A Sørensen
  • Jaakko Tuomilehto
  • Veikko Salomaa
  • Brenda W J H Penninx
  • Eco J C N De Geus
  • Dorret I. Boomsma
  • Terho Lehtimäki
  • Massimo Mangino
  • Markku Laakso
  • Claude Bouchard
  • Nicholas G. Martin
  • Diana Kuh
  • Yongmei Liu
  • Allan Linneberg
  • Winfried März
  • Konstantin Strauch
  • Mika Kivimäki
  • Tamara B. Harris
  • Vilmundur Gudnason
  • Henry Völzke
  • Lu Qi
  • Marjo Riitta Järvelin
  • John C. Chambers
  • Jaspal S. Kooner
  • Philippe Froguel
  • Charles Kooperberg
  • Peter Vollenweider
  • Göran Hallmans
  • Torben Hansen
  • Oluf Pedersen
  • Andres Metspalu
  • Nicholas J. Wareham
  • Claudia Langenberg
  • David R. Weir
  • David J. Porteous
  • Eric Boerwinkle
  • Daniel I. Chasman
  • Gonçalo R. Abecasis
  • Inês Barroso
  • Mark I. McCarthy
  • Timothy M. Frayling
  • Jeffrey R. O’Connell
  • Cornelia M. van Duijn
  • Michael Boehnke
  • Iris M. Heid
  • Karen L. Mohlke
  • David P. Strachan
  • Caroline S. Fox
  • Ching Ti Liu
  • Joel N. Hirschhorn
  • Robert J. Klein
  • Andrew D. Johnson
  • Ingrid B. Borecki
  • Paul W. Franks
  • Kari E. North
  • L. Adrienne Cupples
  • Ruth J F Loos
  • Tuomas O. Kilpeläinen
  • CHARGE Consortium
  • EPIC-InterAct Consortium
  • PAGE Consortium

Research units

Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Peer-reviewedYes
Original languageEnglish
Article numbere1006528
JournalPLoS Genetics
Volume13
Issue number4
DOIs
StatePublished - 1 Apr 2017


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