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

Abstract

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.

Type Journal
ISBN 1476-4687 (Electronic) 0028-0836 (Linking)
Authors Shungin, D.; Winkler, T. W.; Croteau-Chonka, D. C.; Ferreira, T.; Locke, A. E.; Magi, R.; Strawbridge, R. J.; Pers, T. H.; Fischer, K.; Justice, A. E.; Workalemahu, T.; Wu, J. M.; Buchkovich, M. L.; Heard-Costa, N. L.; Roman, T. S.; Drong, A. W.; Song, C.; Gustafsson, S.; Day, F. R.; Esko, T.; Fall, T.; Kutalik, Z.; Luan, J.; Randall, J. C.; et al.:
Garvan Authors Prof John Eisman
Publisher Name NATURE
Published Date 2015-01-01 00:00:00
Published Volume 518
Published Issue 7538
Published Pages 187-96
URL http://www.ncbi.nlm.nih.gov/pubmed/25673412
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13308_13361/emss-61357.pdf