BIG Faculty Member - Joel Hirschhorn, M.D., Ph.D.

Joel Hirschhorn, M.D., Ph.D.

Department of Genetics

Boston Children's Hospital
Genetics & Endocrinology, CLS 16068
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2129
Fax: 617-730-0856
Visit my lab page here.

In people, most common diseases (such as asthma) 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, and how genetic analysis of polygenic traits can inform population genetic studies. 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. 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 many 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 recently developed genotyping and sequencing approaches to more fully characterize the effects of common and rare variants at these loci.

Last Update: 10/26/2017


For a complete listing of publications click here.



Lohmueller, KE, Pearce, CL, Pike, M, Lander, ES, and Hirschhorn, JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genet. 2003; 33:177-82.

Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 2004; 74:1111-20.

Campbell, CD, Ogburn, EO, Lunetta, KL, Lyon, HN, Freedman, ML, Groop, LC, Altshuler, D, Ardlie, KG and Hirschhorn, JN. Demonstrating stratification in a European-American population. Nature Genet. 2005; 37:868-72.

Drake JA+, Bird C+, Nemesh J+, Thomas DJ+, Newton-Cheh C, Reymond A, Excoffier L, Attar H, Antonarakis SE, Dermitzakis E+, Hirschhorn JN+. Conserved noncoding sequences are selectively constrained and not mutation cold spots. Nature Genet. 2006; 88:223-7.

Lango Allen H et al. Hundreds of variants influence height and cluster in genomic loci and biological pathways. Nature 2010; 467:832-8.

Speliotes E et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genet. 2010; 42:937-48.

Turchin MC+, Chiang CWK+, Palmer CD, Sankararaman S, Reich D, GIANT Consortium, Hirschhorn JN. Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nature Genet., in press 2012.

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