The Genetics of Obesity and Metabolic Traits Program

This is a new program led by Dr. Ruth Loos. The prevalence of obesity and overweight continues to increase worldwide, causing not only serious personal health problems but also imposing a substantial economic burden on societies. Currently, almost 70% of adults in the USA are overweight; half of these adults are obese.

A changing environment that promotes excessive calorie intake and discourages physical activity is undeniably an important cause of the obesity epidemic and related metabolic disease. However, not all of us living in this obesogenic environment gain weight or develop metabolic disease. Some remain healthy and of normal weight. The observation that not everyone responds to the obesogenic environment in the same way suggests that an individual’s susceptibility to gain weight or develop disease is, at least in part, also determined by their genetic make-up. Indeed, family and twin studies have shown that 40 to 70% to the variation in obesity risk in the population, is due to the fact that individuals differ genetically.

The Genetics of Obesity and Related Metabolic Traits Programs aims to identify genes associated with people’s susceptibility to obesity and related metabolic traits to improve our understanding of the underlying biology. In addition, we aim to examine the importance of the genetic susceptibility to public health, whether environmental factors can attenuate this genetic susceptibility, and whether genetic loci allow identifying groups or individuals at-risk, which may eventually lead to stratified or personalized prevention and treatment.

So far, we have mainly used the genome-wide association approach to identify disease-associated genes. This approach was introduced in 2005 and has substantially increased the pace of discoveries, identifying hundreds of loci that are unambiguously associated with a large number of common diseases and traits. For obesity susceptibility, at least 55 genetic loci have so far been identified. Similar significant progress in gene discovery has been reported for related metabolic traits such as type 2 diabetes, glucose levels, lipid levels, and blood pressure. We have contributed to many of these discoveries through our participation in various large-scale and international genetics consortia.

Increasingly, our gene-discovery work also focuses on the identification of low-frequency variants through the exome genotyping (chip) and sequencing projects, not only in individuals of white European ancestry, but also in those of African and Hispanic ancestry. We believe that a comprehensive examination of common and rare variation in large-scale populations of diverse ancestry will shed light on the biological causes that underlie the disproportionate disease burden, which eventually will help tailor prevention and treatment to patient subgroups.

The IPM Biobank Project, currently counting more than 20,000 participants recruited from East Harlem, Central Harlem and the Upper East side, serves as an excellent, data-rich population resource representing the ancestral diversity and disease burden of the local communities in upper Manhattan.