News note: GIANT study homes in on obesity genes

obesity genes
Illustration: Elena Hartley

Yes, some obesity is due to genetics. The largest and most powerful study to date has pinned down 14 variants in 13 genes that carry variations associated with body mass index. They provide new clues as to why some people tend to gain weight and have more trouble losing it. Eight of the variants were in genes not previously tied to human obesity.

The study, published last month, was conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium, an international collaboration involving more than 250 research institutions — the same group that brought us height-related genes last year. It combined genetic data from more than 700,000 people and 125 different studies to find rare or low-frequency genetic variants that tracked with obesity.

The study focused on rarer variants in the coding portions of genes, which helped pinpoint causal genes and also helped discover variants with larger effects that those previously discovered by the GIANT consortium. For example, carriers of a variant in the gene MC4R (which produces a protein that tells the brain to stop eating and to burn more energy) weigh 15 pounds more, on average, than people without the variant.

Computational analysis provided some interesting insights into what the 13 genes do. Some, for example, play a role in brain pathways that affect food intake, hunger and satiety. Other variants affect fat-cell biology and how cells expend energy.

This study provided an important confirmation of the role of the nervous system in body weight regulation,” says Joel Hirschhorn MD, PhD, a pediatric endocrinologist and researcher at Boston Children’s Hospital and the Broad Institute of MIT and Harvard, who co-led the study with Ruth Loos, PhD, of the Icahn School of Medicine at Mount Sinai. “Many of the genes from this study were not known to be associated with obesity, but our computational analysis independently implicates these new genes in strikingly similar neuronal pathways as the genes that emerged from our previous work. In addition, our approach newly highlighted a role for genes known to be important in ‘brown fat,’ a type of fat that burns energy and may help keep people lean.”

The researchers think the new findings could help focus the search for new therapeutic targets in obesity.  Read more in Nature Genetics and this press release from Mount Sinai.