Journal
NATURE
Volume 518, Issue 7538, Pages 187-U378Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature14132
Keywords
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Categories
Funding
- ESRC [ES/J023299/1, ES/F02679X/1] Funding Source: UKRI
- MRC [G1001799, MR/L003120/1, MC_UP_A100_1003, MR/K013351/1, MC_UU_12013/1, MC_PC_U127561128, MC_UU_12015/2, MC_UU_12019/1, G0902037, MR/N01104X/1, G0400491, G1000616, MC_UU_12012/1, G0601261, G0600717, G0601463, MC_UU_12015/5, MC_U106179472, MC_U147585819, MC_UU_12015/1, MC_U147585827, G9521010] Funding Source: UKRI
- British Heart Foundation [RG/08/008/25291, FS/14/55/30806, RG/13/2/30098, RG/08/014/24067, RG/07/008/23674, RG/10/12/28456] Funding Source: researchfish
- Cancer Research UK [14136] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Economic and Social Research Council [ES/F02679X/1, ES/J023299/1] Funding Source: researchfish
- Lundbeck Foundation [R190-2014-3904] Funding Source: researchfish
- Medical Research Council [MC_U147585827, MC_UP_A620_1014, G8802774, MC_UU_12013/1, MR/L003120/1, MC_UU_12011/1, G0401527, MC_UP_A100_1003, MC_U147585824, MR/N01104X/1, MC_U106179471, G1001799, G0400491, MC_CF023241, G9521010, MR/K013351/1, MC_U106179472, G0601463, MC_UU_12015/5, G0100222, G0600717B, MC_U147585819, MC_UU_12012/5/B, G0600717, G19/35, MC_UU_12015/1, G0601261, G1000616, MC_UU_12019/1, MC_PC_U127561128, G1000143, MR/K006584/1, MR/K011480/1, G0902037, U1475000001, MC_UU_12012/1, MC_UU_12015/2] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10082, NF-SI-0611-10099, NF-SI-0611-10170, NF-SI-0512-10165, NF-SI-0513-10085, NF-SI-0512-10135, NF-SI-0507-10380, NF-SI-0513-10109, NF-SI-0611-10219, NF-SI-0512-10114, NF-SI-0514-10027, NF-SI-0512-10113] Funding Source: researchfish
- NNF Center for Basic Metabolic Research [Pers Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF14OC0011039, NNF13OC0005785, NNF12OC1016167, NNF12OC1016467, NNF15OC0016416, NNF11OC1014855, NNF13OC0005781, NNF14OC0010513] Funding Source: researchfish
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Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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