Neil Risch

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Neil Risch

Neil Risch is an American human geneticist and professor at the University of California, San Francisco (UCSF). Risch is the Lamond Family Foundation Distinguished Professor in Human Genetics, Founding Director of the Institute for Human Genetics, and Professor of Epidemiology and Biostatistics at UCSF. He specializes in statistical genetics, genetic epidemiology and population genetics.

Risch received undergraduate training in mathematics at the California Institute of Technology (1972) and his PhD in biomathematics at UCLA (1979). Prior to his position at UCSF, he held professorial positions at Columbia University, Yale University and Stanford University. He has been referred to as "the statistical geneticist of our time."[1]

Known for his work on numerous genetic diseases including torsion dystonia, Risch emphasizes the links between population genetics and clinical application, believing that understanding human population history and disease susceptibility go hand in hand.[2]

Population genetics[edit]

Risch has conducted significant work on the nature of human differences on a geographical scale. For instance, he used social and genetic data to analyse genetic admixture from White, African, and Native American ancestry in Puerto Rico, as well as relating this to geographical variation in social status.[3]

Risch considers that genetic drift is a more compelling explanation for the carrier frequency of lysosomal storage diseases in Ashkenazi Jews than heterozygote advantage, in light of analysis of the results of recent genetic testing by his collaborators and himself.[4]

After mapping torsion dystonia by linkage disequilibrium (LD) analysis he found it was genetically dominant and was a founder mutation. Other work has focused on the genetic basis of Parkinson's disease, hemochromatosis, multiple sclerosis, diabetes, autism, epilepsy and hypertension.

Group structure[edit]

Risch has worked on the genetic structure of human groups, for instance multiple levels of structure above the level of the individual increasing in scale up to the level of race. He has translated these results into theoretical impacts on, for instance, rate of decay of linkage disequilibrium, and practical application in personalised medicine. For instance, using the Framingham data, he showed that population stratification leads not only to fewer heterozygotes than predicted from Hardy–Weinberg equilibrium but also to spouses sharing genotypes at all ancestrally informative markers, accounted for by ancestry-related assortative mating in the previous generation.[5]

Psychiatric disease[edit]

In a small twin study on Autism (around 50 twin pairs for each disease and zygosity), he argued these disorders may be less heritable than previously considered, implicating a significant family-level environment effect.[6] Similar findings were observed in family studies[7]


Risch has been a prominent critic of studies on the role of genetics in sexual orientation.[8] In 1999, with colleagues he published a sib-pair study that failed to replicate a previously observed linkage [9] between male sexual orientation and Xq28 DNA markers.[10] While an independent study also found evidence at the same Xq28 location,[11] more recent very large studies failed to produce any evidence of a genetic effect in this region of the X chromosome.[12] Risch also discussed ethical issues underlying studies of socially significant traits and the under-representation of minority scientists in human genetics in his 2015 ASHG Presidential Address,[13] which received a standing ovation.[14]

Genome-wide Association Studies[edit]

With his colleague Kathleen Merikangas, Risch is possibly best known for introducing the concept of genome-wide association studies for the discovery and characterization of genetic variants of modest effects underlying complex diseases.[15] That insight revolutionized the field of human genetics, leading to a large number of genome-wide association studies and the discovery of thousands of genetic variants underlying a broad range of diseases and traits.

Risch is also known, with his colleague Catherine Schaefer, for pioneering the linkage of genome-wide genotype data to electronic health records in a large health provider database (at Kaiser Permanente Northern California), which also demonstrated the power of genome-wide association studies on a large scale.[16]


Risch has received numerous awards and recognition for his scholarship. He is an elected fellow of the American Association for the Advancement of Science (2010), the California Academy of Science (2011), and a member of the National Academy of Medicine (2010). He was the 2015 President of the American Society of Human Genetics, the 2004 recipient of the Curt Stern Award (now the Scientific Achievement Award) from the American Society of Human Genetics and the 2023 recipient of the Lifetime Achievement Award (formerly the William Allan Award) from the American Society of Human Genetics, to date the only individual to have received both. He was also the 2022 recipient of the Paul Hoch Award from the American Psychopathological Association.


  1. ^ Gitschier, Jane (2005-07-25). "The Whole Side of It—An Interview with Neil Risch". PLOS Genetics. 1 (1): e14. doi:10.1371/journal.pgen.0010014. ISSN 1553-7404. PMC 1183530. PMID 17411332.
  2. ^ Risch et al. 2002
  3. ^ Via, Marc; Gignoux, Christopher R.; Roth, Lindsey A.; Fejerman, Laura; Galanter, Joshua; Choudhry, Shweta; Toro-Labrador, Gladys; Viera-Vera, Jorge; Oleksyk, Taras K.; Beckman, Kenneth; Ziv, Elad; Risch, Neil; Burchard, Esteban González; Martínez-Cruzado, Juan Carlos (2011). "History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico". PLOS ONE. 6 (1): e16513. Bibcode:2011PLoSO...616513V. doi:10.1371/journal.pone.0016513. PMC 3031579. PMID 21304981.
  4. ^ Risch N, Tang H, Katzenstein H, Ekstein J (2003). "Geographic distribution of disease mutations in the Ashkenazi Jewish population supports genetic drift over selection". American Journal of Human Genetics. 72 (4): 812–822. doi:10.1086/373882. PMC 1180346. PMID 12612865.
  5. ^ Sebro, Ronnie; Hoffman, Thomas J.; Lange, Christoph; Rogus, John J.; Risch, Neil J. (2010). "Testing for non-random mating: Evidence for ancestry-related assortative mating in the Framingham heart study". Genetic Epidemiology. 34 (7): 674–679. doi:10.1002/gepi.20528. PMC 3775670. PMID 20842694.
  6. ^ Hallmayer, Joachim; Cleveland, S.; Torres, A.; Phillips, J.; Cohen, B.; Torigoe, T.; Miller, J.; Fedele, A.; Collins, J.; Smith, K.; Lotspeich, L.; Croen, L. A.; Ozonoff, S.; Lajonchere, C.; Grether, J. K.; Risch, N. (2011). "Genetic Heritability and Shared Environmental Factors Among Twin Pairs with Autism". Archives of General Psychiatry. 68 (11): 1095–102. doi:10.1001/archgenpsychiatry.2011.76. PMC 4440679. PMID 21727249.
  7. ^ Risch, Neil; Hoffmann, Thomas J.; Anderson, Meredith; Croen, Lisa A.; Grether, Judith K.; Windham, Gayle C. (November 2014). "Familial Recurrence of Autism Spectrum Disorder: Evaluating Genetic and Environmental Contributions". American Journal of Psychiatry. 171 (11): 1206–1213. doi:10.1176/appi.ajp.2014.13101359. ISSN 0002-953X. PMID 24969362.
  8. ^ Risch, Neil; Squires-Wheeler, Elizabeth; Keats, Bronya J. B. (1993-12-24). "Male Sexual Orientation and Genetic Evidence". Science. 262 (5142): 2063–2065. Bibcode:1993Sci...262.2063R. doi:10.1126/science.8266107. ISSN 0036-8075. PMID 8266107.
  9. ^ Hamer, D.; Hu, S; Magnuson, V.; Hu, N; Pattatucci, A. (1993). "A linkage between DNA markers on the X chromosome and male sexual orientation". Science. 261 (5119): 321–7. Bibcode:1993Sci...261..321H. doi:10.1126/science.8332896. PMID 8332896.
  10. ^ Rice G, Anderson C, Risch N, Ebers G (April 1999). "Male homosexuality: absence of linkage to microsatellite markers at Xq28". Science. 284 (5414): 665–7. Bibcode:1999Sci...284..665R. doi:10.1126/science.284.5414.665. PMID 10213693.
  11. ^ Sanders, A. R.; Martin, E. R.; Beecham, G. W.; Guo, S; Dawood, K; Rieger, G; Badner, J. A.; Gershon, E. S.; Krishnappa, R. S.; Kolundzija, A. B.; Duan, J; Gejman, P. V.; Bailey, J. M. (2015). "Genome-wide scan demonstrates significant linkage for male sexual orientation". Psychological Medicine. 45 (7): 1379–88. doi:10.1017/S0033291714002451. PMID 25399360. S2CID 4027333.
  12. ^ Ganna, Andrea; Verweij, Karin J. H.; Nivard, Michel G.; Maier, Robert; Wedow, Robbee; Busch, Alexander S.; Abdellaoui, Abdel; Guo, Shengru; Sathirapongsasuti, J. Fah; 23andMe Research Team; Lichtenstein, Paul; Lundström, Sebastian; Långström, Niklas; Auton, Adam; Harris, Kathleen Mullan (2019-08-30). "Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior". Science. 365 (6456). doi:10.1126/science.aat7693. ISSN 0036-8075. PMC 7082777. PMID 31467194.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  13. ^ "ASHG 2015 Annual Meeting".
  14. ^ Pham, Xuan (2015-10-23). "Highlights from the 2015 American Society of Human Genetics Conference | Biomedical Odyssey". Retrieved 2024-01-11.
  15. ^ Risch, Neil; Merikangas, Kathleen (1996-09-13). "The Future of Genetic Studies of Complex Human Diseases". Science. 273 (5281): 1516–1517. Bibcode:1996Sci...273.1516R. doi:10.1126/science.273.5281.1516. ISSN 0036-8075. PMID 8801636. S2CID 5228523.
  16. ^ Kvale, Mark N; Hesselson, Stephanie; Hoffmann, Thomas J; Cao, Yang; Chan, David; Connell, Sheryl; Croen, Lisa A; Dispensa, Brad P; Eshragh, Jasmin; Finn, Andrea; Gollub, Jeremy; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Lao, Richard (2015-08-01). "Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort". Genetics. 200 (4): 1051–1060. doi:10.1534/genetics.115.178905. ISSN 1943-2631. PMC 4574249. PMID 26092718.

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