An international consortium of scientists have adding six new genetic variants to the two already linked to higher body mass index (BMI). The study also strongly confirmed the role for the two genetic variants identified last year near the FTO and MC4R genes, the investigators report.
Many of the newly discovered genes are active in the central nervous system, positing they may exert their effects via the brain. “One of the interesting things is that the genes near these variants are all active in the central nervous system, suggesting that inherited variation in appetite regulation may have something to do with people’s predisposition to obesity,” says Joel Hirschhorn M.D., Ph.D. of Children's Hospital Boston and the Broad Institute of Harvard and MIT, who led the study together with researchers from the University of Michigan and research institutes in Oxford and Cambridge, U.K.
The team compared their results with those from another large genome-wide association study of BMI, led by deCODE Genetics in Iceland. All the variants were strongly confirmed through deCODE’s data where comparisons were possible, according to the researchers.
The investigators used genetic information from over 32,000 people of European ancestry drawn from 15 genome-wide association studies of BMI involving a total of 76 international research institutes. First there was a large-scale statistical analysis comparing BMI data with about 2.4 million genetic variations, followed by validation of the most promising results in an additional 59,000 individuals.
The effect of each individual variant was modest, ranging from 0.06 to 0.33 BMI units. The investigators estimate that the 1% of people with the most obesity-causing variants will be on average 10 pounds heavier than the 1% of people with the fewest variants and four pounds heavier than the typical person.
The group points out that they have likely uncovered just a fraction of what is probably hundreds of genetic regions that each make small contributions to obesity. They say that identifying new regions will require both larger studies and additional approaches.
The consortium, called GIANT, is now performing large-scale studies to identify more genetic variants contributing to the risk of obesity in both adults and children. They hope to determine whether genetic variants have the same effects in different ethnic populations, in each gender, and in individuals with extreme obesity compared to overweight or normal weight individuals. “The next round of studies will involve new collaborators and DNA from more than 100,000 people,” says Hirschhorn.
The study appears online December 14 in Nature Genetics.