Scientists have discovered genetic variants that increase the risk of obesity and insulin resistance in the general population, according to two studies published online in Nature Genetics. Until now only one locus (FTO) has been associated convincingly with increased risk of obesity.
A consortium of investigators led by Mark McCarthy, Ines Barroso and Nicholas Wareham analyzed the genomes of more than 90,000 individuals and found that a variant near MC4R, encoding the melanocortin-4 receptor, increases susceptibility to obesity. Previous studies had shown that the melanocortin-4 receptor is expressed in neurons in the hypothalamus and is a key regulator of food intake and energy expenditure. Although it is unclear how this variant affects MC4R expression or function, the fact that mutations in the gene are known to cause rare cases of severe childhood obesity lends confidence to the association.
In a separate study, Jaspal Kooner and colleagues carried out a genome-wide scan of several thousand individuals of Indian Asian or European ancestry, and identified a variant near MC4R as increasing risk of obesity and insulin resistance. The risk variant was more frequent in individuals of Indian Asian ancestry, which the authors suggest may account for the increased burden of obesity in Indian Asians.
Mark McCarthy (University of Oxford, UK)
Inês Barroso (Wellcome Trust Sanger Institute, Hinxton, UK)
Nicholas Wareham (Addenbrooke's Hospital, Cambridge, UK)
Jaspal Kooner (Imperial College London, UK)
Abstracts available online:
(C) Nature Genetics press release.
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