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

ADIPOGen Consortium; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GEFOS Consortium; GENIE Consortium; GLGC; ICBP; International Endogene Consortium; LifeLines Cohort Study; MAGIC Investigators; MuTHER Consortium; PAGE Consortium; ReproGen Consortium

研究成果: Article査読

646 被引用数 (Scopus)

抄録

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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed 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.

本文言語English
ページ(範囲)187-196
ページ数10
ジャーナルNature
518
7538
DOI
出版ステータスPublished - 2015 2 12

ASJC Scopus subject areas

  • General

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