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

Research output: Contribution to journalArticle

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.

Details

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 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
  • Paul W. Franks
  • CHARGE Consortium
  • EPIC-InterAct Consortium
  • PAGE Consortium
Organisations
External organisations
  • Yeshiva University
  • Howard University
  • Cornell University
  • University of Essex
  • Friedrich Schiller University Jena
  • Karolinska Institutet
  • University of Washington
  • University of North Carolina
  • University of Cambridge
  • University of Regensburg
  • Brigham and Women's Hospital / Harvard Medical School
  • University of Oxford
  • University College London
  • Framingham Heart Study
  • Boston University
  • Harvard University
  • Uppsala University
  • University of Copenhagen
  • Steno Diabetes Center Copenhagen
  • Umeå University
  • King's College London
  • National Institutes of Health, United States
  • Icahn School of Medicine at Mount Sinai
  • Northwestern University Feinberg School of Medicine
  • Lausanne University Hospital
  • Swiss Institute of Bioinformatics
  • University of Edinburgh
  • Imperial College London
  • Ealing Hospital
  • University of Michigan
  • University of Tartu
  • Fred Hutchinson Cancer Research Center
  • European Genome Institute for Diabetes (EGID) UMR 8199
  • University Medicine Greifswald
  • German Centre for Cardiovascular Research
  • Icelandic Heart Association
  • University of Iceland
  • Heidelberg University
  • Wake Forest University
  • QIMR Berghofer Medical Research Institute
  • Fimlab Laboratories
  • University of Tampere
  • Chinese University of Hong Kong
  • VU University Medical Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Physiotherapy
Original languageEnglish
Article numbere1006528
JournalPLoS Genetics
Volume13
Issue number4
Publication statusPublished - 2017 Apr 1
Publication categoryResearch
Peer-reviewedYes