Genetic studies of body mass index yield new insights for obesity biology

Adam E. Locke, Bratati Kahali, Sonja I. Berndt, Anne E. Justice, Tune H. Pers, Felix R. Day, Corey Powell, Sailaja Vedantam, Martin L. Buchkovich, Jian Yang, Damien C. Croteau-Chonka, Tonu Esko, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Zoltán Kutalik, Jian'an Luan, Reedik Mägi, Joshua C. Randall, Thomas W. WinklerAndrew R. Wood, Tsegaselassie Workalemahu, Jessica D. Faul, Jennifer A. Smith, Jing Hua Zhao, Wei Zhao, Jin Chen, Rudolf Fehrmann, Åsa K. Hedman, Juha Karjalainen, Ellen M. Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L. Bolton, Jennifer L. Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Georg B. Ehret, Bjarke Feenstra, Mary F. Feitosa, Krista Fischer, Anuj Goel, Jian Gong, Anne U. Jackson, Stavroula Kanoni, Marcus E. Kleber, Elina Hyppönen, The LifeLines Cohort Study, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium

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Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalNature
Volume518
Issue number7538
DOIs
Publication statusPublished or Issued - 12 Feb 2015

ASJC Scopus subject areas

  • General

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