An international consortium has made significant inroads into uncovering the genetic basis of obesity by identifying 18 new gene sites associated with overall obesity and 13 that affect fat distribution. The studies include data from nearly a quarter of a million participants, the largest genetic investigation of human traits to date. The papers, both from the GIANT (Genetic Investigation of ANthropometric Traits) consortium which consists of more than 400 scientists from 280 research institutions worldwide will appear in Nature Genetics and are receiving early online publication.
Joel Hirschhorn, MD, PhD of Children's Hospital Boston and the Broad Institute, a senior author on the overall obesity paper and involved in both, says, "Different people have different susceptibilities to obesity. Some don't rigorously watch what they eat or how much they exercise and still resist gaining weight, while others constantly struggle to keep their weight from skyrocketing. Some of this variability is genetic, and our goal was to increase understanding of why different people have different inherited susceptibility to obesity." Because most of the genes newly implicated in these studies have never been suspected of having a role in obesity, findings from both papers begin to shed light on the underlying biology, which may lead to better categorization and treatment of obesity in the future, Hirschhorn notes.
The overall obesity study looked for genetic determinants of body mass index (BMI), calculated as an individual's weight in kilograms over height in meters squared. Investigators combined data from 46 studies involving nearly 124,000 people and confirmed the top results in almost 126,000 more individuals to identify a total of 32 sites consistently associated with BMI, 18 of which are new. One of the novel variants is in the gene encoding for a receptor protein that responds to signals from the gut to influence insulin levels and metab
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Massachusetts General Hospital