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

Shungin, D and Winkler, TW and Croteau-Chonka, DC and Ferreira, T and Locke, AE and Mägi, R and Strawbridge, RJ and Pers, TH and Fischer, K and Justice, AE and Workalemahu, T and Wu, JMW and Buchkovich, ML and Heard-Costa, NL and Roman, TS and Drong, AW and Song, C and Gustafsson, S and Day, FR and Esko, T and Fall, T and Kutalik, Z and Luan, J and Randall, JC and Scherag, A and Vedantam, S and Wood, AR and Chen, J and Fehrmann, R and Karjalainen, J and Kahali, B and Liu, CT and Schmidt, EM and Absher, D and Amin, N and Anderson, D and Beekman, M and Bragg-Gresham, JL and Buyske, S and Demirkan, A and Ehret, GB and Feitosa, MF and Goel, A and Jackson, AU and Johnson, T and Kleber, ME and Kristiansson, K and Mangino, M and Leach, IM and Medina-Gomez, C and Palmer, CD and Pasko, D and Pechlivanis, S and Peters, MJ and Prokopenko, I and Stančáková, A and Sung, YJ and Tanaka, T and Teumer, A and Van Vliet-Ostaptchouk, JV and Yengo, L and Zhang, W (2015) 'New genetic loci link adipose and insulin biology to body fat distribution.' Nature, 518 (7538). 187 - 196. ISSN 0028-0836

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Abstract

© 2015, Macmillan Publishers Limited. All rights reserved. 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.

Item Type: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 28 Sep 2015 10:32
Last Modified: 17 Aug 2017 17:32
URI: http://repository.essex.ac.uk/id/eprint/15076

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