Joel Hirschhorn, MD, PhD

Institution: Children's Hospital
Research: From Genetics to Biology of Obesity, Height, Diabetic Kidney Disease, and Other Polygenic Traits
Grants & Publications: Harvard Catalyst
Categories: Children's

I am a human geneticist and clinically active pediatric endocrinologist and have a long and successful track record in research. My group uses genetics to identify and understand the causal biology of polygenic diseases and traits. My main areas of focus relate to endocrinology, including two major unmet medical needs (obesity and diabetic kidney disease), height (the classical model polygenic trait), and metabolomics. Over the last decade, our work has provided multiple insights into the genetics of obesity and other polygenic traits, and provided early, compelling genetic evidence for two different signatures of recent human evolution/selection.

I have substantial expertise in human genetics and an extensive track record of productivity that has had an impact on the field. I was an early leader in shaping the design of genome-wide association studies (GWAS) showing that meta-analysis of genetic association studies with stringent statistical thresholds would be a successful route to robust genetic associations1,2. I organized and continue to lead the GIANT consortium, which has discovered nearly all the variants known to be associated with measures of obesity and height). I co- lead the GENIE consortium, which has discovered the common variants known to be associated with kidney disease in individuals with type 1 diabetes5,6.

We have developed computational methods that integrate multiple data types to translate genetic discoveries into new biologic insights. We have also developed methods that allow us to extend metabolomics to unknown signals from untargeted profiling data9 and have combined genetic and metabolomics data to study causal relationships with diet, obesity, and diabetes related outcomes. We are now performing genetic studies of rarer variation in large populations and individual families, including whole exome and whole genome sequencing, and studies of metabolite levels and their relationship to obesity. We are also engaged in functional follow up of genes and variants emerging from GWAS. My lab has discovered multiple new genes and rare variants that are responsible for single gene disorders related to pediatric endocrine phenotypes. I have mentored >25 trainees, with consistently successful publication records and career trajectories.