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

CHARGE Consortium; EPIC-InterAct Consortium; PAGE Consortium

doi:10.1371/journal.pgen.1006528

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

CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

146 Scopus citations

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.

Original language	English (US)
Article number	e1006528
Journal	PLoS genetics
Volume	13
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1006528
State	Published - Apr 2017

Funding

We have read the journal's policy and the authors of this manuscript have the following competing interests: Genotyping in the Ely and Fenland studies was supported in part by an MRC-GlaxoSmithKline pilot programme grant (G0701863). The RISC Study was supported in part by AstraZeneca. The D.E.S.I.R. study has been supported in part by INSERM contracts with Lilly, Novartis Pharma, Sanofi-Aventis, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche, and Topcon. In SHIP, genome-wide data have been supported in part by a joint grant from Siemens Healthcare, Erlangen, Germany.

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pgen.1006528

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@article{72553b6fec3246589498d355640cae50,

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

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.",

author = "{CHARGE Consortium} and {EPIC-InterAct Consortium} and {PAGE Consortium} and Mariaelisa Graff and Scott, {Robert A.} and Justice, {Anne E.} and Young, {Kristin L.} and Feitosa, {Mary F.} and Llilda Barata and Winkler, {Thomas W.} and Chu, {Audrey Y.} and Anubha Mahajan and David Hadley and Luting Xue and Tsegaselassie Workalemahu and Heard-Costa, {Nancy L.} and {den Hoed}, Marcel and Ahluwalia, {Tarunveer S.} and Qibin Qi and Ngwa, {Julius S.} and Frida Renstr{\"o}m and Lydia Quaye and Eicher, {John D.} and Hayes, {James E.} and Marilyn Cornelis and Zoltan Kutalik and Elise Lim and Jian{\textquoteright}an Luan and Huffman, {Jennifer E.} and Weihua Zhang and Wei Zhao and Griffin, {Paula J.} and Toomas Haller and Shafqat Ahmad and Marques-Vidal, {Pedro M.} and Stephanie Bien and Loic Yengo and Alexander Teumer and Smith, {Albert Vernon} and Meena Kumari and Harder, {Marie Neergaard} and Justesen, {Johanne Marie} and Kleber, {Marcus E.} and Mette Hollensted and Kurt Lohman and Rivera, {Natalia V.} and Whitfield, {John B.} and Zhao, {Jing Hua} and Stringham, {Heather M.} and Lyytik{\"a}inen, {Leo Pekka} and Charlotte Huppertz and Gonneke Willemsen and Rasmussen-Torvik, {Laura J.}",

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doi = "10.1371/journal.pgen.1006528",

language = "English (US)",

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AU - EPIC-InterAct Consortium

AU - PAGE Consortium

AU - Graff, Mariaelisa

AU - Scott, Robert A.

AU - Justice, Anne E.

AU - Young, Kristin L.

AU - Feitosa, Mary F.

AU - Barata, Llilda

AU - Winkler, Thomas W.

AU - Chu, Audrey Y.

AU - Mahajan, Anubha

AU - Hadley, David

AU - Xue, Luting

AU - Workalemahu, Tsegaselassie

AU - Heard-Costa, Nancy L.

AU - den Hoed, Marcel

AU - Ahluwalia, Tarunveer S.

AU - Qi, Qibin

AU - Ngwa, Julius S.

AU - Renström, Frida

AU - Quaye, Lydia

AU - Eicher, John D.

AU - Hayes, James E.

AU - Cornelis, Marilyn

AU - Kutalik, Zoltan

AU - Lim, Elise

AU - Luan, Jian’an

AU - Huffman, Jennifer E.

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AU - Griffin, Paula J.

AU - Haller, Toomas

AU - Ahmad, Shafqat

AU - Marques-Vidal, Pedro M.

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AU - Teumer, Alexander

AU - Smith, Albert Vernon

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AU - Harder, Marie Neergaard

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AU - Hollensted, Mette

AU - Lohman, Kurt

AU - Rivera, Natalia V.

AU - Whitfield, John B.

AU - Zhao, Jing Hua

AU - Stringham, Heather M.

AU - Lyytikäinen, Leo Pekka

AU - Huppertz, Charlotte

AU - Willemsen, Gonneke

AU - Rasmussen-Torvik, Laura J.

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N2 - 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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Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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