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

Authors:
Mariaelisa Graff Robert A Scott Anne E Justice Kristin L Young Mary F Feitosa Llilda Barata 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 Yu-Ching 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 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 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 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 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

PLoS Genet 2017 Apr 27;13(4):e1006528. Epub 2017 Apr 27.

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.

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.

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http://dx.plos.org/10.1371/journal.pgen.1006528
Publisher Site
http://dx.doi.org/10.1371/journal.pgen.1006528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407576PMC

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April 2017
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