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

Dmitry Shungin, Thomas W. Winkler, Damien C. Croteau-Chonka, Teresa Ferreira, Adam E. Locke, Reedik Mägi, Rona J. Strawbridge, Tune H. Pers, Krista Fischer, Anne E. Justice, Tsegaselassie Workalemahu, Joseph M.W. Wu, Martin L. Buchkovich, Nancy L. Heard-Costa, Tamara S. Roman, Alexander W. Drong, Ci Song, Stefan Gustafsson, Felix R. Day, Tonu EskoTove Fall, Zoltán Kutalik, Jian’an Luan, Joshua C. Randall, André Scherag, Sailaja Vedantam, Andrew R. Wood, Jin Chen, Rudolf Fehrmann, Juha Karjalainen, Bratati Kahali, Ching Ti Liu, Ellen M. Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L. Bragg-Gresham, Steven Buyske, Ayse Demirkan, Georg B. Ehret, Mary F. Feitosa, Anuj Goel, Anne U. Jackson, Toby Johnson, Marcus E. Kleber, Kati Kristiansson, Massimo Mangino, Irene Mateo Leach, Elina Hyppönen, The LifeLines Cohort Study, The ADIPOGen Consortium, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC, The ICBP, The International Endogene Consortium, The MAGIC Investigators, The MuTHER Consortium, The PAGE Consortium, The ReproGen Consortium

Research output: Contribution to journalArticle

601 Citations (Scopus)

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, 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.

Original languageEnglish
Pages (from-to)187-196
Number of pages10
JournalNature
Volume518
Issue number7538
DOIs
Publication statusPublished - 12 Feb 2015

ASJC Scopus subject areas

  • General

Cite this

Shungin, D., Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Locke, A. E., Mägi, R., ... The ReproGen Consortium (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196. https://doi.org/10.1038/nature14132