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

TitleGenome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
Publication TypeJournal Article
Year of Publication2017
AuthorsGraff M, Scott RA, Justice AE, et al.
Secondary AuthorsKilpeläinen TO
Corporate AuthorsCHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium
JournalPLoS Genet
Volume13
Issue4
Paginatione1006528
Date Published2017 Apr
ISSN1553-7404
KeywordsAdiposity, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Mass Index, Epigenomics, Exercise, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Obesity, Waist Circumference, Waist-Hip Ratio
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.

DOI10.1371/journal.pgen.1006528
Alternate JournalPLoS Genet
PubMed ID28448500
PubMed Central IDPMC5407576
Grant ListR01 DK093757 / DK / NIDDK NIH HHS / United States
K99 HL130580 / HL / NHLBI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
MR/K002414/1 / / Medical Research Council / United Kingdom
T32 EY022303 / EY / NEI NIH HHS / United States
MC_UU_12015/3 / / Medical Research Council / United Kingdom
KL2 TR001109 / TR / NCATS NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
MC_UU_12019/1 / / Medical Research Council / United Kingdom
MC_U106179473 / / Medical Research Council / United Kingdom
S10 OD018522 / OD / NIH HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_UU_12015/2 / / Medical Research Council / United Kingdom
P30 DK072488 / DK / NIDDK NIH HHS / United States
MC_UU_12013/1 / / Medical Research Council / United Kingdom
P30 DK020541 / DK / NIDDK NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
RG/10/12/28456 / / British Heart Foundation / United Kingdom