摘要:
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.附注:
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Nicholas JLangenberg, ClaudiaWeir, David RPorteous, David JBoerwinkle, EricChasman, Daniel ICHARGE ConsortiumEPIC-InterAct ConsortiumPAGE ConsortiumAbecasis, Goncalo RBarroso, InesMcCarthy, Mark IFrayling, Timothy MO'Connell, Jeffrey Rvan Duijn, Cornelia MBoehnke, MichaelHeid, Iris MMohlke, Karen LStrachan, David PFox, Caroline SLiu, Ching-TiHirschhorn, Joel NKlein, Robert JJohnson, Andrew DBorecki, Ingrid BFranks, Paul WNorth, Kari ECupples, L AdrienneLoos, Ruth J FKilpelainen, Tuomas OR01 DK093757/DK/NIDDK NIH HHS/K99 HL130580/HL/NHLBI NIH HHS/P30 ES010126/ES/NIEHS NIH HHS/MR/K002414/1/Medical Research Council/United KingdomT32 EY022303/EY/NEI NIH HHS/KL2 TR001109/TR/NCATS NIH HHS/R01 DK072193/DK/NIDDK NIH HHS/MC_UU_12019/1/Medical Research Council/United KingdomS10 OD018522/OD/NIH HHS/R01 HL105756/HL/NHLBI NIH HHS/MC_UU_12015/2/Medical Research Council/United KingdomP30 DK072488/DK/NIDDK NIH HHS/P30 DK020541/DK/NIDDK NIH HHS/UM1 CA182913/CA/NCI NIH HHS/P30 DK020572/DK/NIDDK NIH HHS/S10 OD020069/OD/NIH HHS/P2C HD050924/HD/NICHD NIH HHS/RG/10/12/28456/British Heart Foundation/United KingdomPLoS Genet. 2017 Apr 27;13(4):e1006528. doi: 10.1371/journal.pgen.1006528. eCollection 2017 Apr.