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

AE Locke, B Kahali, MAGIC Collaboration, SI Berndt, AE Justice, TH Pers, R Felix, C Powell, S Vedantam, ML Buchkovich, Jiaqi Yang, DC Croteau-Chonka, T Esko, T Fall, T Ferreira, S Gustafsson, Z Kutalik, JA Luan, R Magi, JC RandallTW Winkler, AR Wood, T Workalemahu, JD Faul, Najaf Amin, M Beekman, Ayse Demirkan, K (Kirsten) Fischer, Maria Medina Gomez, Marjolein Peters, S Trompet, Sander Laan, Aaron Isaacs, Karol Estrada Gil, JJ (Jouke Jan) Hottenga, IM (Ilja) Nolte, Frank Verhulst, N (Niek) Verweij, Lisette Stolk, AC Heath, OH Franco Duran, Bert Hofman, AJ (A.) Oldehinkel, RP (Ronald) Stolk, JCM Witteman, M.C. Zillikens, Ben Oostra, Fernando Rivadeneira, TD Spector, André Uitterlinden, Ruth J.F. Loos, K Speliotes

Research output: Contribution to journalArticleAcademicpeer-review

2631 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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 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 systemin 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

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