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Neil Risch, PhD

Neil Risch, PhD
Professor and Director, Institute for Human Genetics
Research Summary:
Human Genetics, Population Genetics, Statistical Genetics, Genetic Epidemiology

Dr. Risch, a statistical geneticist, genetic epidemiologist, and population geneticist is involved in a variety of projects of both a theoretical and applied nature. These studies include both clinical and population genetic projects.  He has developed novel tools and approaches for the mapping and identification of genetic variants underlying both Mendelian and non-Mendelian diseases.  For example, he contributed to the cloning of genes for torsion dystonia and hemochromatosis.  He defined admixture mapping in ethnically admixed populations as a tool for gene discovery and has applied it to such diseases as hypertension and lipidemia.  In collaboration with his colleague Kathleen Merikangas, he proposed genome-wide association studies as the next generation tool after linkage analysis for identifying novel disease susceptibility variants; this approach, now applied on a large scale, has identified thousands of novel disease and trait-related genetic variants.  Over the past decade, Dr. Risch has collaborated with colleagues at Kaiser Permanente Northern California Division of Research (where he holds an adjunct appointment) to develop a large cohort combining electronic health record information with environmental and genomic data for genetic epidemiology research related to aging.  The cohort contains approximately 110,000 individuals with genome-wide genotype and telomere length data, and has been the basis for a variety of genetic studies related to cardiovascular, metabolic and cancer outcomes.  He is also currently active in genetic epidemiologic studies of autism spectrum disorder, utilizing a large cohort of affected families identified through state of California record linkage databases.  In the realm of population genetics, he has characterized the role of ancestry in mate selection and its impact on genetic patterns of linkage disequilibrium in the population over time.  He has developed novel methods for estimating kinship in admixed populations, and also described methods of admixture analysis in populations which have undergone significant genetic drift, such as the Ashkenazi Jewish population.

Selected Publications

Risch, N.  Linkage strategies for genetically complex traits. I. Multi-locus models, Am J Hum Genet 46:222-228, 1990.

Risch, N.  Linkage strategies for genetically complex traits. II. The power of affected relative pairs, Am J Hum Genet 46:229-241, 1990.

Risch, N., Devlin, B.  On the probability of matching DNA Fingerprints, Science 255:717-720, 1992.

Risch, N., Zhang, H.  Extreme discordant sib-pairs for mapping quantitative trait loci in humans, Science 268:1584-1589, 1995.

Feder, J.N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D.A., Basava, A., Dormishian, F., Domingo, R., Ellis, M.C., Fullan, A., Hinton, L.M.,  Jones, N.L., Kimmel, B.E., Kronmal, G.S., Lauer, P., Lee, V.K., Loeb, D.B., Mapa, F.A., McClelland, E., Meyer, N.c., Mintier, G.A., Moeller, N., Moore, T., Morikang, E., Prass, C.E., Quintana, L., Starnes, S.M., Schatzman, R.C., Brunke, K.J., Drayna, D.T., Risch, N.J., Bacon, B.R., Wolff, R.K.  “A novel MHC class 1-like gene is mutated in patients with hereditary haemochromatosis.” Nat Genet 13:399-408, 1996.

Risch, N., Merikangas, K.  “The future of genetic studies of complex human diseases.” Science 273:1516-1517, 1996.

Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., Nguyen, L., Yang, J., Harper, C., Thorpe, D., Vermeer, S., Young, H., Hebert, J., Lin, A., Ferguson, J., Chiotti, C., Wiese-Slater, S., Rogers, T., Salmon, B., Nicholas, P., Myers, R.M.  “A genomic screen of autism: evidence for a multilocus etiology.” Am J Hum Genet 65:493-507, 1999.

Risch, N.J.  Searching for genetic determinants in the new millennium, Nature 405:847-856, 2000.

Risch, N., Tang, H., Katzenstein, H., Ekstein, J.  Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection, Am J Hum Genet 72:812-822, 2003.

Kim, U.K., Jorgenson, E., Coon, H., Leppert, M., Risch, N., Drayna, D.  Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide, Science 299:1221-1225, 2003.

Botstein, D., Risch, N.  Discovering genotypes underlying human phenotypes:  past successes for mendelian disease, future approaches for complex disease, Nat Genet 33:228-237, 2003.

Zhu, X., Luke, A., Cooper, R.S., Quertermous, T., Hanis, C., Mosley, T., Gu, C.C., Tang, H., Rao, D.C., Risch, N., Weder, A.  Admixture mapping for hypertension loci with genome-scan markers, Nat Genet 37(2):177-81, 2005.

Tang, H., Coram, M., Wang, P., Zhu, X., Risch, N.  Reconstructing genetic ancestry blocks in admixed individuals, Am J Hum Genet 79:1-12, 2006.

Risch N, Choudhry S, Via M, Basu A, Sebro R, Eng C, Beckman K, Thyne S, Chapela R, Rodriguez-Santana JR, Rodriguez-Cintron W, Avila PC, Ziv E, Burchard EG. “Ancestry-related assortative mating in Latino populations.”  Genome Biol 10:R132, 2009.

Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR.  Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta analysis, JAMA 301:2462-71, 2009.

Hoffmann TJ, Kvale MN, Hesselson SE, Zhan Y, Aquino C, Cao Y, Cawley S, Chung E, Connell S, Eshragh J, Ewing M, Gollub J, Henderson M, Hubbell E, Iribarren C, Kaufman J, Lao RZ, Lu Y, Ludwig D, Mathauda GK, McGuire W, Mei G, Miles S, Purdy MM, Quesenberry C, Ranatunga D, Rowell S, Sadler M, Shapero MH, Shen L, Shenoy TR, Smethurst D, Van den Eeden SK, Walter L, Wan E, Wearley R, Webster T, Wen CC, Weng L, Whitmer RA, Williams A, Wong SC, Zau C, Finn A, Schaefer C, Kwok PY, Risch N. Next generation genome wide association tool: design and coverage of a high-throughput European-optimized SNP array, Genomics 98:79-89, 2011.

Hoffmann TJ, Zhan Y, Kvale MN, Hesselson SE, Gollub J, Iribarren C, Lu Y, Mei G, Purdy MM, Quesenberry C, Rowell S, Shapero MH, Smethurst D, Somkin CP, Van den Eeden SK, Walter L, Webster T, Whitmer RA, Finn A, Schaefer C, Kwok PY, Risch N. Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm. Genomics 98:422-430, 2011.

Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N. “Genetic heritability and shared environmental factors among twin pairs with autism.” Arch Gen Psychiatry 68:1095-1102, 2011.

Thornton T, Tang H, Hoffmann TJ, Ochs-Balcom HM, Caan BJ, Risch N. “Estimating kinship in admixed populations”  Am J Hum Genet 91:122-138, 2012.