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

Graff, M; Scott, RA; Justice, AE; Young, KL; Feitosa, MF; Barata, L; Winkler, TW; Chu, AY; Mahajan, A; Hadley, D; et al. 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; Rivera, NV; Whitfield, JB; Zhao, JH; Stringham, HM; Lyytikäinen, L-P; Huppertz, C; Willemsen, G; Peyrot, WJ; Wu, Y; Kristiansson, K; Demirkan, A; Fornage, M; Hassinen, M; Bielak, LF; Cadby, G; Tanaka, T; Mägi, R; van der Most, PJ; Jackson, AU; Bragg-Gresham, JL; Vitart, V; Marten, J; Navarro, P; Bellis, C; Pasko, D; Johansson, Å; Snitker, S; Cheng, Y-C; Eriksson, J; Lim, U; Aadahl, M; Adair, LS; Amin, N; Balkau, B; Auvinen, J; Beilby, J; Bergman, RN; Bergmann, S; Bertoni, AG; Blangero, J; Bonnefond, A; Bonnycastle, LL; Borja, JB; Brage, S; Busonero, F; Buyske, S; Campbell, H; Chines, PS; Collins, FS; Corre, T; Smith, GD; Delgado, GE; Dueker, N; Dörr, M; Ebeling, T; Eiriksdottir, G; Esko, T; Faul, JD; Fu, M; Færch, K; Gieger, C; Gläser, S; Gong, J; Gordon-Larsen, P; Grallert, H; Grammer, TB; Grarup, N; van Grootheest, G; Harald, K; Hastie, ND; Havulinna, AS; Hernandez, D; Hindorff, L; Hocking, LJ; Holmens, OL; Holzapfel, C; Hottenga, JJ; Huang, J; Huang, T; Hui, J; Huth, C; Hutri-Kähönen, N; James, AL; Jansson, J-O; Jhun, MA; Juonala, M; Kinnunen, L; Koistinen, HA; Kolcic, I; Komulainen, P; Kuusisto, J; Kvaløy, K; Kähönen, M; Lakka, TA; Launer, LJ; Lehne, B; Lindgren, CM; Lorentzon, M; Luben, R; Marre, M; Milaneschi, Y; Monda, KL; Montgomery, GW; De Moor, MHM; Mulas, A; Müller-Nurasyid, M; Musk, AW; Männikkö, R; Männistö, S; Narisu, N; Nauck, M; Nettleton, JA; Nolte, IM; Oldehinkel, AJ; Olden, M; Ong, KK; Padmanabhan, S; Paternoster, L; Perez, J; Perola, M; Peters, A; Peters, U; Peyser, PA; Prokopenko, I; Puolijoki, H; Raitakari, OT; Rankinen, T; Rasmussen-Torvik, LJ; Rawal, R; Ridker, PM; Rose, LM; Rudan, I; Sarti, C; Sarzynski, MA; Savonen, K; Scott, WR; Sanna, S; Shuldiner, AR; Sidney, S; Silbernagel, G; Smith, BH; Smith, JA; Snieder, H; Stančáková, A; Sternfeld, B; Swift, AJ; Tammelin, T; Tan, S-T; Thorand, B; Thuillier, D; Vandenput, L; Vestergaard, H; van Vliet-Ostaptchouk, JV; Vohl, M-C; Völker, U; Waeber, G; Walker, M; Wild, S; Wong, A; Wright, AF; Zillikens, MC; Zubair, N; Haiman, CA; Lemarchand, L; Gyllensten, U; Ohlsson, C; Hofman, A; Rivadeneira, F; Uitterlinden, AG; Pérusse, L; Wilson, JF; Hayward, C; Polasek, O; Cucca, F; Hveem, K; Hartman, CA; Tönjes, A; Bandinelli, S; Palmer, LJ; Kardia, SLR; Rauramaa, R; Sørensen, TIA; Tuomilehto, J; Salomaa, V; Penninx, BWJH; de Geus, EJC; Boomsma, DI; Lehtimäki, T; Mangino, M; Laakso, M; Bouchard, C; Martin, NG; Kuh, D; Liu, Y; Linneberg, A; März, W; Strauch, K; Kivimäki, M; Harris, TB; Gudnason, V; Völzke, H; Qi, L; Järvelin, M-R; Chambers, JC; Kooner, JS; Froguel, P; Kooperberg, C; Vollenweider, P; Hallmans, G; Hansen, T; Pedersen, O; Metspalu, A; Wareham, NJ; Langenberg, C; Weir, DR; Porteous, DJ; Boerwinkle, E; Chasman, DI; CHARGE Consortium; EPIC-InterAct Consortium; PAGE Consortium; Abecasis, GR; Barroso, I; McCarthy, MI; Frayling, TM; O'Connell, JR; van Duijn, CM; Boehnke, M; Heid, IM; Mohlke, KL; Strachan, DP; Fox, CS; Liu, C-T; Hirschhorn, JN; Klein, RJ; Johnson, AD; Borecki, IB; Franks, PW; North, KE; Cupples, LA; Loos, RJF; Kilpeläinen, TO (2017) Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults. PLoS Genet, 13 (4). e1006528. ISSN 1553-7404 https://doi.org/10.1371/journal.pgen.1006528
SGUL Authors: Strachan, David Peter

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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.

Item Type: Article
Additional Information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
Keywords: Developmental Biology, 0604 Genetics
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: PLoS Genet
ISSN: 1553-7404
Language: eng
Dates:
DateEvent
27 April 2017Published
7 December 2016Accepted
Publisher License: Creative Commons: Public Domain Dedication
Projects:
Project IDFunderFunder ID
UNSPECIFIEDArthritis Research UKhttp://dx.doi.org/10.13039/501100000341
RG/10/12/28456British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
SP/04/002British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
UNSPECIFIEDCancer Research UKhttp://dx.doi.org/10.13039/501100000289
G0701863Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
084723/Z/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
088869/B/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_U106179471Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0500539Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0600705Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0601966Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0700931Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1002319Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
K013351Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12019/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 28448500
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108539
Publisher's version: https://doi.org/10.1371/journal.pgen.1006528

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