Researchers from Icahn School of Medicine at Mount Sinai, participating in the largest genetic study yet on obesity, have helped uncover stronger links between genes and body weight and body fat distribution.
The trailblazing discoveries were published in two companion papers in the February issue of the journal Nature, and were the result of a four-year international research project conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Other key participating institutions included the Broad Institute of the Massachusetts Institute of Technology and Harvard University, the University of Michigan Health System, and the University of North Carolina School of Medicine.
“Our goal was to get a better understanding of the genes and biological pathways that influence obesity,” says Ruth Loos, PhD, Professor of Preventive Medicine at The Mount Sinai Hospital, Director of the Genetics of Obesity and Related Metabolic Traits Program in the Charles Bronfman Institute for Personalized Medicine, and a senior author who coordinated the collection and interpretation of data for the meta-analysis of both studies. Among the data sources was the Mount Sinai BioMe™ Biobank, which collects de-identified DNA and plasma used for a variety of research purposes from consenting patients.
Researchers analyzed genetic data from nearly 340,000 individuals to understand why some individuals gain weight more easily than others and why some people tend to store excess fat at their waists, whereas others at their hips. Findings revealed there are more than 140 locations across the genome that play roles in various obesity traits.
In the first research project, scientists examining the link between genes and body mass index (BMI) identified 97 sites across the human genome associated with obesity—triple the number previously known. “The next critical step is determining which genes in the neighborhood of each of them actually cause an increased susceptibility to obesity,” observes Dr. Loos. “That will require input from scientists with a wide range of expertise before our findings can be used toward targeted obesity prevention or treatment strategies.”
The BMI researchers also found that susceptibility to weight gain has a neurological—and not just a metabolic—component. “Many of the genes for obesity seem to be playing a role in the brain, where we believe they regulate food intake and influence appetite, hunger, and reward,” notes Dr. Loos.
The second research project pinpointed 49 sites on the genome associated with waist-to-hip ratio, a measure of body fat distribution. Individuals with greater amounts of belly fat are more likely to suffer from metabolic conditions such as type 2 diabetes and cardiovascular disease than those whose fat is distributed throughout the body. Figuring out which genes influence the specific areas where fat is deposited would help scientists better understand the biology behind these metabolic conditions.
Still, while genes are important, Dr. Loos emphasizes they are not the only factor in determining body weight. “Being physically active and maintaining a healthy diet can substantially reduce your genetic susceptibility to gain weight,” she says.