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

ADIPOGen Consortium, ReproGen Consortium, The CARDIOGRAMplusC4D Consortium, CDKGen Consortium, The GEFOS Consortium, The GENIE Consortium, The GLGC, ICBP Consortium, The International Endogene Consortium, The LifeLines Cohort Study, The MAGIC Investigators, The MuTHER Consortium, The PAGE Consortium, Dmitry Shungin, Thomas W Winkler, Damien C Croteau-Chonka, Teresa Ferreira, Adam E Locke, Reedik Mägi, Rona J StrawbridgeTune 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 Esko, Tove 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, Najaf Amin, Ayse Demirkan, Marjolein J Peters, Alexander Teumer, Aaron Isaacs, Floor van Oort, Niek Verweij, Jing Hua Zhao, John Rb Perry, Lisette Stolk, Albert Hofman, Yongmei Liu, Ben A Oostra, Fernando Rivadeneira, André G Uitterlinden, Cornelia M van Duijn, Jian Yang, M Carola Zillikens, Mark I. McCarthy, Elizabeth K. Speliotes, Kari E. North, Caroline S. Fox, Inês Barroso, Paul W. Franks, Erik Ingelsson, Iris M. Heid, Ruth J.F. Loos, L. Adrienne Cupples, Andrew P. Morris, Cecilia M. Lindgren*, Karen L. Mohlke*, Lisette Stolk, André Uitterlinden, Fernando Rivadeneira, Bert Hofman, OH (Oscar) Franco Duran, JCM Witteman, Karol Estrada Gil

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1077 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)187-196
Number of pages10
Issue number7538
Publication statusPublished - 11 Feb 2015

Research programs

  • EMC COEUR-09
  • EMC MGC-02-96-01
  • EMC MM-01-39-04
  • EMC MM-01-39-09-A
  • EMC MM-01-52-07
  • EMC NIHES-01-64-01
  • EMC NIHES-04-55-01
  • EMC OR-01-39-08


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