Joel N. Hirschhorn, MD, PhD
In people, most common diseases (such as diabetes) and quantitative phenotypes (such as height and weight) are polygenic traits, influenced by multiple genetic and environmental factors. Our laboratory's long-term goal is to understand the genetic basis of human height and weight, as well as other polygenic traits and diseases. We also are interested in how genetic ancestry and human evolutionary history can influence genetic studies of polygenic traits. We study body mass index and other anthropometric measures of obesity because these are heritable and readily measured polygenic risk factors for a number of serious diseases, including diabetes, cancer and heart disease. We study height (stature) because of its relevance to human growth and development, and also because it is a classic polygenic trait through which we and others have learned a lot about the genetic architecture of human polygenic traits. Although our main focus is on obesity and height, the lab also has projects related to other diseases (asthma, diabetic kidney disease, sickle cell disease) and quantitative traits (timing of puberty). We also embark on computational projects related to polygenic traits. Our lab collaborates with investigators at the Broad Institute in many of these areas. Recently, the main focus in the lab has been to use genome-wide association data at millions of variants across the genome to identify new loci associated with obesity and height. We have successfully identified hundreds of novel associations between common genetic variants and both height and obesity. We plan to continue to search for new loci that influence obesity and height, and also to characterize further the loci we have helped to discover using genetic, computational and functional approaches. We are using next generation sequencing technology to more fully characterize the effects of common and rare variants at these loci.