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

ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, ICBP Consortium, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The GENIE Consortium, The International Endogene Consortium, Adam E Locke, Bratati Kahali, The LifeLines Cohort Study, ReproGen Consortium, Sonja I Berndt, Anne E Justice, Tune H Pers, Felix R DayCorey 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 Winkler, Andrew 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, Ayse Demirkan, Marjolein J Peters, Alexander Teumer, Sander W van der Laan, Aaron Isaacs, Jouke-Jan Hottenga, Frank C Verhulst, Niek Verweij, John R B Perry, Lisette Stolk, Albert Hofman, M Carola Zillikens, Yongmei Liu, Ben A Oostra, Fernando Rivadeneira, André G Uitterlinden, Cornelia M van Duijn, Oscar Franco Duran, JCM Witteman, Maria Medina Gomez, Karol Estrada Gil, Ruth J.F. Loos, EK Speliotes

Research output: Contribution to journalArticleAcademicpeer-review

3086 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 - 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-01-64-02
  • EMC NIHES-04-55-01
  • EMC OR-01-39-08

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