University of California, San Francisco  |  About UCSF  |  Search UCSF  |  UCSF Medical Center  |  Log In

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 and genetic epidemiologist, is involved in a variety of projects of both a theoretical and applied nature. These studies include both clinical and population genetic projects. For example, one study involves identification of genes underlying the torsion dystonias. To date, Dr. Risch and his collaborators have identified several genes for specific subtypes of idiopathic dystonia , yet a number of variant forms remain unmapped. Current research involves additional mapping and positional cloning of these variant forms. Dr. Risch has also collaborated in large, multi-site projects on genetic susceptibility to hypertension and cardiovascular disease endpoints. These projects involve linkage analysis, positional cloning, and population based association studies. One of these studies recently led to the identification of regions on chromosomes 6 and 21 by admixture linkage disequilibrium analysis in African American subjects with hypertension. Dr. Risch plans to expand the admixture studies to other cardiovascular and metabolic phenotypes in both African American and Hispanic study subjects. He has a longstanding collaborative project underway, with Canadian colleagues, on genetic susceptibility to multiple sclerosis. These studies investigate both genetic and environmental hypotheses. In the genetics realm of this project , he continues to examine linkage and positional cloning projects on over 1,000 multi-case families and undertake new candidate gene studies as well as linkage disequilibrium approaches. A major focus will continue on the examination of genetic contributions of the HLA region. He is collaborating with Drs. Kathleen Giacomini (UCSF) and Catherine Schaefer at Kaiser on pharmacogenetics of membrane transporters and, specifically, their role in response to antidepressant medications. He has several ongoing population genetic studies that examine the relationship between genetic variation and social categorizations such as race and ethnicity, and the importance of these relationships for identifying genetic factors underlying common and complex diseases, as well as rarer, Mendelian forms. He is also collaborating on genetics projects of autism and Crohn's Disease as well as genetic disorders in the Jewish population.

Selected Publications

Risch, N., Devlin, B. (1995) Linkage disequilibrium measures for fine-scale mapping. Genomics 29:311-322.

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

Ebers, G. C., Sadovnick, A. D. & Risch, N. (1995) A genetic basis for familial aggregation in multiple sclerosis. Nature 377:150-151.

Schwab, S. G., Albus, M., Hallmayer, J., Honig, S., Boormann, M., Lichtermann, D., Ebstein, R. P., Avnon, M., Ley-Reuss, E., Ackenheil, M., Minges, J., Lerer, B., Risch, N., Maier, W., and Wildenauer, D. B. (1995) Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by affected sib pair linkage analysis. Nat. Genet. 11:325-327.

Sadovnick, A. D., Ebers, G. C., Dyment, D., and Risch, N. (1996) Evidence for the genetic basis in multiple sclerosis. Lancet 347:1728-1730.

Hanis, C. L., Boerwinkle, E., Chakraborty, R., Ellsworth, D. L., Concannon, P., Stirling, B., Morrison, V. A., Waplehorst, B., Spielman, R. S., Goglin-Ewins, K. J., Shepard, J. M., Williams, S. R., Risch, N., Hinds, D., Iwasaki, N., Ogata, M., Omori, Y., Petzold, C., Rietzsch, H., Schroeder, H.-E., Schulze, J., Cox, N. J., Menzel, S., Borirau, V. V., Yamagata, K., Yang, Y. and Bell, G. I. (1996) A genome-wide search for human non-insulin-dependent (type 2) diabetes mellitus susceptibility genes: evidence for a major susceptibility locus on chromosome 2. Nat. Genet. 13:1161-166.

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., Kromal, 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., and Wolff, R. K. (1996) A novel MHC class 1-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13:399-408.

Ebers. G. C., Kukay, D., Bulman, D. E., Sadovnick, A. D., Rice, G., Anderson, C., Armstrong, H., Cousin, K., Bell, R. B., Hader, W., Paty, D. W., Hashimoto, S., Oger, J., Duquette, P., Warren, S., Gray, T., O'Connor, P., Nath, A., Auty, A., Metz, L., Francis, G., Paulseth, J. E., Murray, T. J., Pryse-Phillips, W., Nelson, R., Freedman, M., Brunet, D., Bouchard, J.-P., Hinds, D., and Risch, N. (1996) A full genome search in multiple sclerosis. Nat. Genet. 13:472-476.

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

Mansfield, T. A., Simon, D. B., Farfel, Z., Bia, M., Tucci, J. R., Lebel, M., Gutkin, M., Vialettes, B., Chris tofilis, M. A., Kauppiunen-Makelin, R., Mayan, H., Risch, N., and Lifton, R. P. (1997) Multilocus linkage of familial hyperkalemia and hypertension, pseudohypoadlosteronism type II, to 1q31-42 and 17p[11-q21. Nat. Genet. 16:202-205.

Ozelius, L. J., Hewett, J. W., Page, C. E., Bressman, S. B., Kramer, P. L., Shalish, C., deLeon, D., Brin, M. F., Raymond, D., Corey, D. P., Fahn, S., Risch, N. J., Buckler, A. J., Gusella, J. F., and Breakefield, X. O. (1997) The early onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat. Genet. 17:40-48.

Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., Myers, R. H, Pericak-Vance, M. A., Risch, N., vanDuijn, C. M. (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. ApoE and Alzheimer Disease Meta Analysis Consortium. JAMA 278:1349-1356.

Risch, N. (1997) Haemochromatosis, Hfe and genetic complexity. (1997) Nat. Genet. 17:375-376.

Concannon, P., Gglin-Ewins, K. J., Hinds, D., Wapelhorst, B., Morrison, V. A., Stirling, B., Mitra, M., Farmer, J., Williams, S. R., Cox, N. J., Bell, G. I., Risch, N., and Speilman, R. S. (1998) A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus. Nat. Genet. 19:292-296.

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

Risch., N. (2001) The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiol. Biomarkers Prev. 10:733-741.

Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Perez-Stable EJ, Sheppard D, Risch N. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med. 2003 Mar 20;348(12):1170-5.

McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C, Cavalli-Sforza LL, Barsh GS, Hallmayer JF, Underhill PA, Risch NJ, Freeman GJ, DeKruyff RH, Umetsu DT. Immunology: hepatitis A virus link to atopic disease. Nature. 2003 Oct 9;425(6958):576.

Tang H, Quertermous T, Rodriguez B, Kardia SL, Zhu X, Brown A, Pankow JS, Province MA, Hunt SC, Boerwinkle E, Schork NJ, Risch NJ. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies. Am J Hum Genet. 2005 Feb;76(2):268-75. Epub 2004 Dec 29.

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