Joel Naom Hirschhorn

Joel Naom Hirschhorn

Concordia Professor of Pediatrics
Joel Naom Hirschhorn

There are clear resemblances between parents and children for height, weight, and many other traits and diseases; these familial resemblances are influenced strongly by inherited genetic factors. Most common diseases (such as diabetes, obesity, or asthma) and quantitative traits (such as height and weight) are polygenic, meaning they are influenced by the likely additive effects of multiple genetic factors. Our laboratory's long-term goal is to use human genetics to identify the genetic factors contributing to human height and weight, as well as other polygenic traits and diseases, and to translate these genetic results into biological insights. 

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 important 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. To study height and obesity, our lab helps lead the Genetic Investigation of ANthropometric Traits (GIANT) consortium, which uses genome-wide association studies and other methods to discover common genetic variants that influence anthropometric traits like height and weight.  We use the results of these large-scale genetic studies for computational analyses to generate and test biological hypothesis about the regulation of human height and weight. To accomplish this goal, we also develop and implement new computational tools to help translate genetic association into actionable biological hypotheses. 

Although our main focus is on obesity and height, the lab also has projects related to other diseases (such as diabetic kidney disease) and quantitative traits (timing of puberty and metabolite levels). We continue to work in the intersection between population genetics and the genetic analysis of polygenic traits, including studying different signatures of selection. We also generate metabolite profiling data to inform our studies of obesity, and develop and implement tools to use untargeted metabolite profiling to identify predictive and causal biomarkers for disease. 

We are continuing to expand our genetic studies of height and weight (sample sizes currently in the millions), and are focusing on integrating genome-wide association and sequencing data with non-genetic data (RNA sequencing, epigenetics, and metabolite profiling) to generate new hypotheses about causal cell types and biological pathways for height, weight, and other human diseases and traits. We continue to do experimental work using in vitro and in vivo models to test these hypotheses. We also are combining polygenic risk scores, exome or genome sequencing, and clinical phenotypes for insights into disease biology and prediction, and to improve clinical diagnosis of children with endocrine disorders. Our lab collaborates closely with investigators at the Broad Institute in many of these areas.

Contact Information

Boston Children's Hospital
Genetics & Endocrinology, CLS 16028
3 Blackfan Circle
Boston, MA 02115
p: 617-919-2129

Community or Program Affiliation