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. Zhou K, Yee SW, Seiser EL, van Leeuwen N, Tavendale R, Bennett AJ, Groves CJ, Coleman RL, van der Heijden AA, Beulens JW, de Keyser CE, Zaharenko L, Rotroff DM, Out M, Jablonski KA, Chen L, Javorský M, Židzik J, Levin AM, Williams LK, Dujic T, Semiz S, Kubo M, Chien HC, Maeda S, Witte JS, Wu L, Tkác I, Kooy A, van Schaik RH, Stehouwer CD, Logie L. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet. 2016 Aug 8.
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  2. Lee SA, Mefford JA, Huang Y, Witte JS, Martin JN, Haas DW, Mclaren PJ, Mushiroda T, Kubo M, Byakwaga H, Hunt PW, Kroetz DL. Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans. AIDS. 2016 Jul 17; 30(11):1807-15.
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  3. Majumdar A, Haldar T, Witte JS. Determining Which Phenotypes Underlie a Pleiotropic Signal. Genet Epidemiol. 2016 Jul; 40(5):366-81.
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  4. Sapru A, Liu KD, Wiemels J, Hansen H, Pawlikowska L, Poon A, Jorgenson E, Witte JS, Calfee CS, Ware LB, Matthay MA. Association of common genetic variation in the protein C pathway genes with clinical outcomes in acute respiratory distress syndrome. Crit Care. 2016; 20(1):151.
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  5. Uricchio LH, Zaitlen NA, Ye CJ, Witte JS, Hernandez RD. Selection and explosive growth alter genetic architecture and hamper the detection of causal rare variants. Genome Res. 2016 Jul; 26(7):863-73.
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  6. Mosley JD, Witte JS, Larkin EK, Bastarache L, Shaffer CM, Karnes JH, Stein CM, Phillips E, Hebbring SJ, Brilliant MH, Mayer J, Ye Z, Roden DM, Denny JC. Identifying genetically driven clinical phenotypes using linear mixed models. Nat Commun. 2016; 7:11433.
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  7. Carmichael SL, Yang W, Ma C, Roberts E, Kegley S, English P, Lammer EJ, Witte JS, Shaw GM. Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk. Birth Defects Res A Clin Mol Teratol. 2016 Aug; 106(8):653-8.
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  8. Li M, Li J, He Z, Lu Q, Witte JS, Macleod SL, Hobbs CA, Cleves MA. Testing Allele Transmission of an SNP Set Using a Family-Based Generalized Genetic Random Field Method. Genet Epidemiol. 2016 May; 40(4):341-51.
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  9. Gusev A, Shi H, Kichaev G, Pomerantz M, Li F, Long HW, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Zheng W, Pettaway CA, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, John EM, Murphy AB, Signorello LB, Carpten J, Leske MC, Wu SY, Hennis AJ, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Witte JS, Casey G, Kaggwa S, Cook MB, Stram DO, Blot WJ, Eeles RA, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Southey MC, Fitzgerald LM, Gronberg H, Wiklund F, Aly M, Henderson BE, Schleutker J, Wahlfors T, Tammela TL, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah P, Pashayan N, Khaw KT, Stanford JL, Thibodeau SN, McDonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Wokolorczyk D, Kluzniak W, Cannon-Albright L, Teerlink C, Brenner H, Dieffenbach AK, Arndt V, Park JY, Sellers TA, Lin HY, Slavov C, Kaneva R, Mitev V, Batra J, Spurdle A, Clements JA, Teixeira MR, Pandha H, Michael A, Paulo P, Maia S, Kierzek A. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nat Commun. 2016; 7:10979.
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  10. Lindquist KJ, Paris PL, Hoffmann TJ, Cardin NJ, Kazma R, Mefford JA, Simko JP, Ngo V, Chen Y, Levin AM, Chitale D, Helfand BT, Catalona WJ, Rybicki BA, Witte JS. Mutational Landscape of Aggressive Prostate Tumors in African American Men. Cancer Res. 2016 Apr 1; 76(7):1860-8.
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  11. Han Y, Rand KA, Hazelett DJ, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Stanford JL, Zheng W, Schumacher FR, Berndt SI, Wang Z, Xu J, Rohland N, Reich D, Tandon A, Pasaniuc B, Allen A, Quinque D, Mallick S, Notani D, Rosenfeld MG, Jayani RS, Kolb S, Gapstur SM, Stevens VL, Pettaway CA, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, John EM, Murphy AB, Signorello LB, Carpten J, Leske MC, Wu SY, Hennis AJ, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Witte JS, Casey G, Lubwama A, Pooler LC, Sheng X, Coetzee GA, Cook MB, Chanock SJ, Stram DO, Watya S, Blot WJ, Conti DV, Henderson BE, Haiman CA. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. J Natl Cancer Inst. 2016 Jul; 108(7).
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  12. Scarbrough PM, Weber RP, Iversen ES, Brhane Y, Amos CI, Kraft P, Hung RJ, Sellers TA, Witte JS, Pharoah P, Henderson BE, Gruber SB, Hunter DJ, Garber JE, Joshi AD, McDonnell K, Easton DF, Eeles R, Kote-Jarai Z, Muir K, Doherty JA, Schildkraut JM. A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer. Cancer Epidemiol Biomarkers Prev. 2016 Jan; 25(1):193-200.
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  13. Majumdar A, Witte JS, Ghosh S. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance. Genet Epidemiol. 2015 Dec; 39(8):635-50.
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  14. 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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  15. Kwok B, Hall JM, Witte JS, Xu Y, Reddy P, Lin K, Flamholz R, Dabbas B, Yung A, Al-Hafidh J, Balmert E, Vaupel C, El Hader C, McGinniss MJ, Nahas SA, Kines J, Bejar R. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood. 2015 Nov 19; 126(21):2355-61.
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  16. 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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  17. 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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  18. 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, Le Marchand L, 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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  19. 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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  20. 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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