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, Juha Karjalainen, Irene Mateo Leach, Jana V Van Vliet-Ostaptchouk, Marcel Bruinenberg, Catharina A Hartman, Ilja M Nolte, Salome Scholtens, Joanna Smolonska, Morris A Swertz, Niek Verweij, Judith M Vonk, Harm-Jan Westra, Stephan J L Bakker, Ron T Gansevoort, Meena Kumari, Albertine J Oldehinkel, Dirkje S Postma, Ronald P Stolk, Folkert W Asselbergs, Harold Snieder, Pim van der Harst, Lude Franke, Lifelines Cohort Study

Research output: Contribution to journalArticleAcademicpeer-review

1999 Citations (Scopus)

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 - 12-Feb-2015

Keywords

  • GENOME-WIDE ASSOCIATION
  • PROVIDES INSIGHTS
  • GLYCEMIC TRAITS
  • HUMAN HEIGHT
  • LOCI
  • METAANALYSIS
  • VARIANTS
  • EXPRESSION
  • PATHWAYS
  • ARCHITECTURE

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