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Department
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Genetics
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Hospital Title
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Assistant in Medicine
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Academic Title
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Associate Professor of Genetics
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Phone
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617-919-2129
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Fax
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617-730-0253
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Email
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Joel Hirschhorn
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Location
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300 Longwood Avenue
Enders 561
Boston, MA 02115
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The Hirschhorn Laboratory's long-term goal is to understand the genetic basis of obesity and other quantitative measures of growth and development (measures of obesity such as body mass index, height, and pubertal timing). We also study certain common diseases including diabetic nephropathy and asthma. Many different genes and gene variants contribute to these polygenic diseases and traits, as do nongenetic factors such as diet and physical activity. The laboratory studies DNA sequence variants, usually single nucleotide polymorphisms (SNPs), in large, well-characterized patient samples to test for an association with the traits or diseases they study. The goal is to identify new genes and pathways that are important in human obesity and human growth, leading to new biologic insights and potentially guides to new or improved therapies or interventions.
Recently, genomewide association studies of hundreds of thousands of SNPs have become feasible, and permit a powerful, unbiased search for common genetic variants that influence obesity and other polygenic traits and diseases. Dr. Hirschhorn is a leader of an international consortium, GIANT (Genetic Investigation of ANthropometric Traits), whose goal is to find common variants that influence obesity and height by combining genomewide association data. We and our collaborators in GIANT have analyzed whole genome association data to find the first common genetic variants that reliably influences adult height, and this consortium has also recently discovered genetic variants that influence body mass index, leading to new insights into human growth and obesity.
Another major focus of the Hirschhorn Laboratory is understanding -- and avoiding -- the ways in which spurious results can arise in genetic association studies. They 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 how ancestry, ethnicity, and other population genetic factors 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 traits and diseases such as obesity.
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Joel Hirschhorn received his MD degree from Harvard Medical School. He completed an internship, residency, and fellowship in Endocrinology at Children's Hospital Boston and is a Senior Associate Member and Coordinator of the Metabolism Initiative at the Broad Institute of Harvard and MIT.
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- Lohmueller KE, Pearce CL, Pike M, Lander ES, 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 EL, Lunetta KL, Lyon HN, Freedman ML, Groop LC, Altshuler D, Ardlie KG, 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; 38:223-7.
- Diabetes Genetics Initiative. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007; 316:1331-6
- Lyon HN+, Emilsson V+, Hinney A+, Heid IM+, Lasky-Su J+, & Celedon JC*, Wichmann HE*, Hebebrand J*, Stefansson K*, Lange C*, Hirschhorn JN*. The association of a SNP upstream of INSIG2 with Body Mass Index is reproduced in several but not all cohorts. PLoS Genetics 2007; 3:e61.
- Weedon MN+, Lettre G+, Freathy RM+, Lindgren CM+, &, McCarthy MI*, Hirschhorn JN*, Frayling TM*. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genet. 2007; 39:1245-50.
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