New genetic loci link adipose and insulin biology to body fat distribution.

Published

Journal Article

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 × 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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Duke Authors

Cited Authors

  • Shungin, D; Winkler, TW; Croteau-Chonka, DC; Ferreira, T; Locke, AE; Mägi, R; Strawbridge, RJ; Pers, TH; Fischer, K; Justice, AE; Workalemahu, T; Wu, JMW; Buchkovich, ML; Heard-Costa, NL; Roman, TS; Drong, AW; Song, C; Gustafsson, S; Day, FR; Esko, T; Fall, T; Kutalik, Z; Luan, J; Randall, JC; Scherag, A; Vedantam, S; Wood, AR; Chen, J; Fehrmann, R; Karjalainen, J; Kahali, B; Liu, C-T; Schmidt, EM; Absher, D; Amin, N; Anderson, D; Beekman, M; Bragg-Gresham, JL; Buyske, S; Demirkan, A; Ehret, GB; Feitosa, MF; Goel, A; Jackson, AU; Johnson, T; Kleber, ME; Kristiansson, K; Mangino, M; Leach, IM; Medina-Gomez, C; Palmer, CD; Pasko, D; Pechlivanis, S; Peters, MJ; Prokopenko, I; StanĨáková, A; Sung, YJ; Tanaka, T; Teumer, A; Van Vliet-Ostaptchouk, JV; Yengo, L; Zhang, W; Albrecht, E; Ärnlöv, J; Arscott, GM; Bandinelli, S; Barrett, A; Bellis, C; Bennett, AJ; Berne, C; Blüher, M; Böhringer, S; Bonnet, F; Böttcher, Y; Bruinenberg, M; Carba, DB; Caspersen, IH; Clarke, R; Daw, EW; Deelen, J; 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Published Date

  • February 12, 2015

Published In

Volume / Issue

  • 518 / 7538

Start / End Page

  • 187 - 196

PubMed ID

  • 25673412

Pubmed Central ID

  • 25673412

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature14132

Language

  • eng

Conference Location

  • England