Scientists have discovered gene variants associated with increased risk of common obesity in people with European ancestry, reports a study online this week in Nature Genetics. Common forms of obesity are influenced by variants in many genes, each contributing a small amount to an individual’s susceptibility.
Mutations in PCSK1 were previously shown to cause one of the rare forms of obesity that are associated with mutations in a single gene.
Philippe Froguel and colleagues asked whether common variants in PCSK1 predispose to more common, complex forms of obesity, in which multiple genes likely have a role. Three variants that change the sequence of the PCSK1 protein were found more frequently in the genomes of more than 13,000 obese individuals of European ancestry than in the genomes of non-obese controls. These variants were also associated increased risk of childhood obesity. PCSK1 is an enzyme that converts inactive forms of hormones that regulate energy metabolism into active forms. The authors emphasize the need to identify the specific substrates of PCSK1 that are most relevant to the control of body weight.