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.
|Titolo:||Genetic studies of body mass index yield new insights for obesity biology|
|Parole Chiave:||Adipogenesis; Adiposity; Age Factors; Continental Population Groups; Energy Metabolism; Europe; Female; Genetic Predisposition to Disease; Glutamic Acid; Humans; Insulin; Male; Obesity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Synapses; Body Mass Index; Genome-Wide Association Study; Multidisciplinary|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||feb-2015|
|Digital Object Identifier (DOI):||10.1038/nature14177|
|Appare nelle tipologie:||01 - Articolo su periodico|