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

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; Charlotte Huppertz; Gonneke Willemsen; Jouke Jan Hottenga; Yuri Milaneschi; Marleen H M De Moor; Brenda W J H Penninx; Eco J C de Geus; Dorret I Boomsma; CHARGE Consortium

doi:10.1371/journal.pgen.1006528

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

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, Charlotte Huppertz, Gonneke Willemsen, Jouke Jan Hottenga, Yuri Milaneschi, Marleen H M De Moor, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, CHARGE Consortium

Research output: Contribution to Journal › Article › Academic › peer-review

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
Article number	e1006528
Pages (from-to)	e1006528
Journal	PLoS Genetics
Volume	13
Issue number	4
DOIs	https://doi.org/10.1371/journal.pgen.1006528
Publication status	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.

Funders	Funder number
National Institute of Child Health and Human Development
European Commission
AstraZeneca
Seventh Framework Programme	305739, 258753, 339462, 277849, 279143, 201668, 201865, 313010, 201413, 286284, 602633
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK072193, P30DK072488, P30DK020572, R01DK089256, P30DK020541, R01DK093757
???publication-publication-funding-organisation-not-added???	480-01-006
Wellcome Trust	088869, 084723, 091551
???publication-publication-funding-organisation-not-added???	IP-2013-11-8875
National Health and Medical Research Council	442981, 389892, 442915, 389927
Medical Research Council	MR/K013351/1, MC_PC_13046, MC_U106179473, MC_PC_13048, MC_UU_12013/1, MR/K002414/1, MC_UU_12019/1, MC_UU_12015/3, MC_UU_12015/2
National Eye Institute	T32EY022303
National Heart, Lung, and Blood Institute	R01HL105756, K99HL130580, ZIAHL006170
National Institute on Aging	ZIAAG006000, ZIAAG007480, ZIAAG007380
National Center for Advancing Translational Sciences	KL2TR001109
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	122661
NIH Office of the Director	S10OD020069, S10OD018522
Eunice Kennedy Shriver National Institute of Child Health and Human Development	P2CHD050924
National Human Genome Research Institute	ZIAHG000024
Horizon 2020 Framework Programme	692145
UK Research and Innovation	MC_U106179471
National Institute of Environmental Health Sciences	P30ES010126
MRC-GlaxoSmithKline	G0701863
National Cancer Institute	UM1CA182913

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Journal Article

Cohort Studies

Netherlands Twin Register (NTR)

Access to Document

10.1371/journal.pgen.1006528

Persistent URL (handle)

Persistent link

Cite this

Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., Winkler, T. W., Chu, A. Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N. L., den Hoed, M., Ahluwalia, T. S., Qi, Q., Ngwa, J. S., Renström, F., Quaye, L., ... CHARGE Consortium (2017). Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genetics, 13(4), e1006528. Article e1006528. https://doi.org/10.1371/journal.pgen.1006528

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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 \textasciitilde{}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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author = "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'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 Charlotte Huppertz and Gonneke Willemsen and Hottenga, \{Jouke Jan\} and Yuri Milaneschi and \{De Moor\}, \{Marleen H M\} and Penninx, \{Brenda W J H\} and \{de Geus\}, \{Eco J C\} and Boomsma, \{Dorret I\} and \{CHARGE Consortium\}",

year = "2017",

month = apr,

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

language = "English",

volume = "13",

pages = "e1006528",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

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Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, L, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, Q, Ngwa, JS, Renström, F, Quaye, L, Eicher, JD, Hayes, JE, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, W, Zhao, W, Griffin, PJ, Haller, T, Ahmad, S, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Huppertz, C, Willemsen, G, Hottenga, JJ, Milaneschi, Y, De Moor, MHM, Penninx, BWJH, de Geus, EJC , Boomsma, DI & CHARGE Consortium 2017, 'Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults', PLoS Genetics, vol. 13, no. 4, e1006528, pp. e1006528. https://doi.org/10.1371/journal.pgen.1006528

TY - JOUR

T1 - Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

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

AU - Zhang, Weihua

AU - Zhao, Wei

AU - Griffin, Paula J

AU - Haller, Toomas

AU - Ahmad, Shafqat

AU - Marques-Vidal, Pedro M

AU - Bien, Stephanie

AU - Yengo, Loic

AU - Teumer, Alexander

AU - Smith, Albert Vernon

AU - Kumari, Meena

AU - Harder, Marie Neergaard

AU - Justesen, Johanne Marie

AU - Kleber, Marcus E

AU - Hollensted, Mette

AU - Lohman, Kurt

AU - Huppertz, Charlotte

AU - Willemsen, Gonneke

AU - Hottenga, Jouke Jan

AU - Milaneschi, Yuri

AU - De Moor, Marleen H M

AU - Penninx, Brenda W J H

AU - de Geus, Eco J C

AU - Boomsma, Dorret I

AU - CHARGE Consortium

PY - 2017/4

Y1 - 2017/4

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.

AB - 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.

KW - Journal Article

UR - https://www.scopus.com/pages/publications/85018450983

UR - https://www.scopus.com/pages/publications/85018450983#tab=citedBy

U2 - 10.1371/journal.pgen.1006528

DO - 10.1371/journal.pgen.1006528

M3 - Article

C2 - 28448500

SN - 1553-7390

VL - 13

SP - e1006528

JO - PLoS Genetics

JF - PLoS Genetics

IS - 4

M1 - e1006528

ER -

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

Abstract

Funding

UN SDGs

Keywords

Cohort Studies

Access to Document

Persistent URL (handle)

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