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

OnderzoeksoutputAcademicpeer review

2109 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)197-206
Aantal pagina's10
TijdschriftNature
Volume518
Nummer van het tijdschrift7538
DOI's
StatusPublished - 12-feb-2015

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