John S. Witte, PhD

John S. Witte, PhD

Professor, Department of Epidemiology/Biostatistics and Urology, UCSF; Leader, Cancer Genetics Program, UCSF Helen Diller Family Comprehensive Cancer Center

Phone: (415) 502-6882 (voice)
Box 0794, UCSF, San Francisco, CA 94143-0794

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Cancer Center Membership

Program Member » Prostate Cancer» Cancer Genetics

Research Summary

I have extensive experience in the design and statistical analysis of genetic epidemiologic projects. My research program encompasses a synthesis of methodological and applied genetic epidemiology, with the overall aim of deciphering the mechanisms underlying complex diseases and traits. I have developed extensive, widely used methods and software for studying rare genetic variants, pathways, interactions, and genome-wide association studies. I am applying these methods to studies of prostate cancer, birth defects, and pharmacogenomics. My lab has developed extensive methods and software for studying rare genetic variants, pathways, interactions, and genome-wide association studies. For analyzing rare variants, my lab has recently developed novel Bayesian and ‘Step-up’ empirical methods. My work includes showing how hierarchical modeling—a potentially valuable analytic approach—can be used to incorporate existing information to improve estimation. In more applied work, I am presently undertaking studies of the germline and somatic genomic basis of prostate cancer, with a particular focus on disease aggressiveness among understudied populations. Most recently, I am evaluating the use of cell-free DNA (liquid biopsies) for prediction of disease risk and progression. In addition, I direct an NIH-Funded post-Doctoral training grant in Genetic Epidemiology, and have mentored over 40 pre- and post-doctoral fellows.


University of California, Santa Barbara, CA, BS, 1986, Mathematical Sciences
University of California, Berkeley, CA, MS, 1988, Industrial Engineering and Operations Research
University of California, Los Angeles, CA, PhD, 1994, Epidemiology

Professional Experience

  • 1994-1995
    Research Assistant Professor, Department of Preventive Medicine, University of Southern California
  • 1995-1999
    Assistant Professor, Department of Epidemiology and Biostatistics, Case Western Reserve University
  • 1999-2003
    Associate Professor, Department of Epidemiology and Biostatistics, Case Western Reserve University
  • 2003-present
    Professor, Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 2005-present
    Leader, Program in Cancer Genetics and Epidemiology, UC San Francisco
  • 2005-present
    Associate Director, Institute for Human Genetics, UC, San Francisco
  • 2008-present
    Head, Division of Cancer Epidemiology, UC, San Francisco

Honors & Awards

  • 1986
    Undergraduate Honors, University of California, Santa Barbara
  • 1989-1994
    National Research Service Award, NIH
  • 1994
    Ruth F. Richards Outstanding Student Award, UCLA School of Public Health Alumni Association
  • 1999-2000
    Glennan Fellow, Case Western Reserve University
  • 2002-2003
    Visiting Scientist Award, International Agency for Research on Cancer

Selected Publications

  1. Hoffmann TJ, Witte JS. Strategies for Imputing and Analyzing Rare Variants in Association Studies. Trends Genet. 2015 Oct; 31(10):556-63.
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  2. Hung RJ, Ulrich CM, Goode EL, Brhane Y, Muir K, Chan AT, Marchand LL, Schildkraut J, Witte JS, Eeles R, Boffetta P, Spitz MR, Poirier JG, Rider DN, Fridley BL, Chen Z, Haiman C, Schumacher F, Easton DF, Landi MT, Brennan P, Houlston R, Christiani DC, Field JK, Bickeböller H, Risch A, Kote-Jarai Z, Wiklund F, Grönberg H, Chanock S, Berndt SI, Kraft P, Lindström S, Al Olama AA, Song H, Phelan C, Wentzensen N, Peters U, Slattery ML. Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer. J Natl Cancer Inst. 2015 Nov; 107(11).
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  3. Han Y, Hazelett DJ, Wiklund F, Schumacher FR, Stram DO, Berndt SI, Wang Z, Rand KA, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Xu J, Travis RC, Key TJ, Siddiq A, Canzian F, Takahashi A, Kubo M, Stanford JL, Kolb S, Gapstur SM, Diver WR, Stevens VL, Strom SS, Pettaway CA, Al Olama AA, Kote-Jarai Z, Eeles RA, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Isaacs WB, Chen C, Lindstrom S, Le Marchand L, Giovannucci EL, Pomerantz M, Long H, Li F, Ma J, Stampfer M, John EM, Ingles SA, Kittles RA, Murphy AB, Blot WJ, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske MC, Wu SY, Hennis AJ, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Witte JS, Casey G, Riboli E, Li Q, Freedman ML, Hunter DJ, Gronberg H, Cook MB, Nakagawa H, Kraft P, Chanock SJ, Easton DF, Henderson BE, Coetzee GA, Conti DV, Haiman CA. Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions. Hum Mol Genet. 2015 Oct 1; 24(19):5603-18.
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  4. Chen F, He J, Zhang J, Chen GK, Thomas V, Ambrosone CB, Bandera EV, Berndt SI, Bernstein L, Blot WJ, Cai Q, Carpten J, Casey G, Chanock SJ, Cheng I, Chu L, Deming SL, Driver WR, Goodman P, Hayes RB, Hennis AJ, Hsing AW, Hu JJ, Ingles SA, John EM, Kittles RA, Kolb S, Leske MC, Millikan RC, Monroe KR, Murphy A, Nemesure B, Neslund-Dudas C, Nyante S, Ostrander EA, Press MF, Rodriguez-Gil JL, Rybicki BA, Schumacher F, Stanford JL, Signorello LB, Strom SS, Stevens V, Van Den Berg D, Wang Z, Witte JS, Wu SY, Yamamura Y, Zheng W, Ziegler RG, Stram AH, Kolonel LN, Marchand LL, Henderson BE, Haiman CA, Stram DO. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults. PLoS One. 2015; 10(6):e0131106.
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  5. Hoffmann TJ, Van Den Eeden SK, Sakoda LC, Jorgenson E, Habel LA, Graff RE, Passarelli MN, Cario CL, Emami NC, Chao CR, Ghai NR, Shan J, Ranatunga DK, Quesenberry CP, Aaronson D, Presti J, Wang Z, Berndt SI, Chanock SJ, McDonnell SK, French AJ, Schaid DJ, Thibodeau SN, Li Q, Freedman ML, Penney KL, Mucci LA, Haiman CA, Henderson BE, Seminara D, Kvale MN, Kwok PY, Schaefer C, Risch N, Witte JS. A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences. Cancer Discov. 2015 Aug; 5(8):878-91.
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  6. Webber DM, MacLeod SL, Bamshad MJ, Shaw GM, Finnell RH, Shete SS, Witte JS, Erickson SW, Murphy LD, Hobbs C. Developments in our understanding of the genetic basis of birth defects. Birth Defects Res A Clin Mol Teratol. 2015 Aug; 103(8):680-91.
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  7. Tai CG, Graff RE, Liu J, Passarelli MN, Mefford JA, Shaw GM, Hoffmann TJ, Witte JS. Detecting gene-environment interactions in human birth defects: Study designs and statistical methods. Birth Defects Res A Clin Mol Teratol. 2015 Aug; 103(8):692-702.
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  8. Virlogeux V, Graff RE, Hoffmann TJ, Witte JS. Replication and heritability of prostate cancer risk variants: impact of population-specific factors. Cancer Epidemiol Biomarkers Prev. 2015 Jun; 24(6):938-43.
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  9. Helfand BT, Roehl KA, Cooper PR, McGuire BB, Fitzgerald LM, Cancel-Tassin G, Cornu JN, Bauer S, Van Blarigan EL, Chen X, Duggan D, Ostrander EA, Gwo-Shu M, Zhang ZF, Chang SC, Jeong S, Fontham ET, Smith G, Mohler JL, Berndt SI, McDonnell SK, Kittles R, Rybicki BA, Freedman M, Kantoff PW, Pomerantz M, Breyer JP, Smith JR, Rebbeck TR, Mercola D, Isaacs WB, Wiklund F, Cussenot O, Thibodeau SN, Schaid DJ, Cannon-Albright L, Cooney KA, Chanock SJ, Stanford JL, Chan JM, Witte J, Xu J, Bensen JT, Taylor JA, Catalona WJ. Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Hum Genet. 2015 Apr; 134(4):439-50.
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  10. Hoffmann TJ, Sakoda LC, Shen L, Jorgenson E, Habel LA, Liu J, Kvale MN, Asgari MM, Banda Y, Corley D, Kushi LH, Quesenberry CP, Schaefer C, Van Den Eeden SK, Risch N, Witte JS. Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort. PLoS Genet. 2015 Jan; 11(1):e1004930.
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  11. Uricchio LH, Torres R, Witte JS, Hernandez RD. Population genetic simulations of complex phenotypes with implications for rare variant association tests. Genet Epidemiol. 2015 Jan; 39(1):35-44.
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  12. Choudhry S, Baskin LS, Lammer EJ, Witte JS, Dasgupta S, Ma C, Surampalli A, Shen J, Shaw GM, Carmichael SL. Genetic Polymorphisms in ESR1 and ESR2 Genes, and Risk of Hypospadias in a Multiethnic Study Population. J Urol. 2015 May; 193(5):1625-31.
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  13. Zaitlen N, Pasaniuc B, Sankararaman S, Bhatia G, Zhang J, Gusev A, Young T, Tandon A, Pollack S, Vilhjálmsson BJ, Assimes TL, Berndt SI, Blot WJ, Chanock S, Franceschini N, Goodman PG, He J, Hennis AJ, Hsing A, Ingles SA, Isaacs W, Kittles RA, Klein EA, Lange LA, Nemesure B, Patterson N, Reich D, Rybicki BA, Stanford JL, Stevens VL, Strom SS, Whitsel EA, Witte JS, Xu J, Haiman C, Wilson JG, Kooperberg C, Stram D, Reiner AP, Tang H, Price AL. Leveraging population admixture to characterize the heritability of complex traits. Nat Genet. 2014 Dec; 46(12):1356-62.
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  14. Chen HS, Hutter CM, Mechanic LE, Amos CI, Bafna V, Hauser ER, Hernandez RD, Li C, Liberles DA, McAllister K, Moore JH, Paltoo DN, Papanicolaou GJ, Peng B, Ritchie MD, Rosenfeld G, Witte JS, Gillanders EM, Feuer EJ. Genetic simulation tools for post-genome wide association studies of complex diseases. Genet Epidemiol. 2015 Jan; 39(1):11-9.
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  15. Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, Shui IM, Chen YC. Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis. PLoS One. 2014; 9(10):e110569.
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  16. Gerstenberger JP, Bauer SR, Van Blarigan EL, Sosa E, Song X, Witte JS, Carroll PR, Chan JM. Selenoprotein and antioxidant genes and the risk of high-grade prostate cancer and prostate cancer recurrence. Prostate. 2015 Jan; 75(1):60-9.
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  17. Bhatia G, Tandon A, Patterson N, Aldrich MC, Ambrosone CB, Amos C, Bandera EV, Berndt SI, Bernstein L, Blot WJ, Bock CH, Caporaso N, Casey G, Deming SL, Diver WR, Gapstur SM, Gillanders EM, Harris CC, Henderson BE, Ingles SA, Isaacs W, De Jager PL, John EM, Kittles RA, Larkin E, McNeill LH, Millikan RC, Murphy A, Neslund-Dudas C, Nyante S, Press MF, Rodriguez-Gil JL, Rybicki BA, Schwartz AG, Signorello LB, Spitz M, Strom SS, Tucker MA, Wiencke JK, Witte JS, Wu X, Yamamura Y, Zanetti KA, Zheng W, Ziegler RG, Chanock SJ, Haiman CA, Reich D, Price AL. Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture. Am J Hum Genet. 2014 Oct 2; 95(4):437-44.
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  18. Witte JS, Visscher PM, Wray NR. The contribution of genetic variants to disease depends on the ruler. Nat Rev Genet. 2014 Nov; 15(11):765-76.
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  19. Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Røder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokolorczyk D, Kluzniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet. 2014 Oct; 46(10):1103-9.
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  20. Rosenstein BS, West CM, Bentzen SM, Alsner J, Andreassen CN, Azria D, Barnett GC, Baumann M, Burnet N, Chang-Claude J, Chuang EY, Coles CE, Dekker A, De Ruyck K, De Ruysscher D, Drumea K, Dunning AM, Easton D, Eeles R, Fachal L, Gutiérrez-Enríquez S, Haustermans K, Henríquez-Hernández LA, Imai T, Jones GD, Kerns SL, Liao Z, Onel K, Ostrer H, Parliament M, Pharoah PD, Rebbeck TR, Talbot CJ, Thierens H, Vega A, Witte JS, Wong P, Zenhausern F. Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys. 2014 Jul 15; 89(4):709-13.
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