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 metabolism. Another variant is near a gene known to encode proteins affecting appetite.
The second study looked at genetic associations with how fat is distributed in the body.
Studies have shown that fat stored in the abdomen increases the risk of type 2 diabetes and heart disease, even after adjusting for obesity. In contrast, fat stored in the hips and thighs may actually protect against diabetes and high blood pressure. The investigators examined the genetic determinants of waist-to-hip ratio, a measure of fat distribution, analyzing data from 77,000 participants in 32 studies. The regions identified in this analysis were then checked against data from another 29 studies including over 113,500 individuals. This revealed 14 gene regions associated with waist-to-hip ratio, adding 13 new regions and confirming the one previously known association.
“By finding genes that have an important role in influencing fat distribution and the ways in which that differs between men and women, we hope to home in on the crucial underlying biological processes,” says Cecilia Lindgren, PhD, of the Wellcome Trust Centre for Human Genetics at Oxford University, senior researcher on the waist-to-hip ratio study, who was involved in both papers.
Source: Massachusetts General Hospital, USA