Program in Genomics

Joel Hirschhorn, MD, PhD

Assistant Professor of Genetics and Pediatrics

The Hirschhorn laboratory's long-term goal is to understand the genetic basis of quantitative measures related to body size (measures of obesity, height, and pubertal timing) and certain common diseases (diabetic nephropathy and asthma). These traits and diseases are all polygenic complex traits, meaning that many different genes and gene variants play a role (as do nongenetic factors such as diet and physical activity). Our laboratory studies DNA sequence variants, usually single nucleotide polymorphisms, or SNPs, and genotypes these variants in large, well-characterized patient samples to test for an association with the traits or diseases we study.

Recently, whole genome association studies have become feasible, and permit a powerful, unbiased search for common genetic variants that influence polygenic traits and diseases. We have analyzed whole genome association data to help find the first common genetic variant that reliably influences adult height, and are currently analyzing similar data to search for additional height genes, as well as genes influencing obesity, timing of puberty, asthma, and diabetic nephropathy.

Another major focus of the Hirschhorn laboratory is understanding -- and avoiding -- the ways in which spurious results can arise in genetic association studies. We performed a meta-analysis of association studies that suggested that rigorous statistical criteria and adequate power were critical to interpreting association study results. We have also studied the effects of population genetics on association studies. Specifcally, we have studied the relatively recent impact of evolution, through selective pressure, on allele frequencies in different populations, and how differences across populations can influence association studies.

Finally, we have an interest in the genetics of gene expression and how this can be used to localize which genes are influenced by variants that alter human quantitative traits and disease risk.

Additional Information

Go to Children's Hospital Research.

Go to the Hirschhorn Laboratory Website.

Projects

Diabetes