University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
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

Cancer Center Program Memberships

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.

Education

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. Zhang C, de Smith AJ, Smirnov IV, Wiencke JK, Wiemels JL, Witte JS, Walsh KM. Non-additive and epistatic effects of HLA polymorphisms contributing to risk of adult glioma. J Neurooncol. 2017 Jul 18.
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  2. Mosley JD, Shoemaker MB, Wells QS, Darbar D, Shaffer CM, Edwards TL, Bastarache L, McCarty CA, Thompson W, Chute CG, Jarvik GP, Crosslin DR, Larson EB, Kullo IJ, Pacheco JA, Peissig PL, Brilliant MH, Linneman JG, Witte JS, Denny JC, Roden DM. Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes. Circ Cardiovasc Genet. 2017 Apr; 10(2).
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  3. Hoffman JD, Graff RE, Emami NC, Tai CG, Passarelli MN, Hu D, Huntsman S, Hadley D, Leong L, Majumdar A, Zaitlen N, Ziv E, Witte JS. Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk. PLoS Genet. 2017 Mar; 13(3):e1006690.
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  4. Hoffmann TJ, Passarelli MN, Graff RE, Emami NC, Sakoda LC, Jorgenson E, Habel LA, Shan J, Ranatunga DK, Quesenberry CP, Chao CR, Ghai NR, Aaronson D, Presti J, Nordström T, Wang Z, Berndt SI, Chanock SJ, Mosley JD, Klein RJ, Middha M, Lilja H, Melander O, Kvale MN, Kwok PY, Schaefer C, Risch N, Van Den Eeden SK, Witte JS. Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer. Nat Commun. 2017 Jan 31; 8:14248.
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  5. Emami NC, Leong L, Wan E, Van Blarigan EL, Cooperberg MR, Tenggara I, Carroll PR, Chan JM, Witte JS, Simko JP. Tissue Sources for Accurate Measurement of Germline DNA Genotypes in Prostate Cancer Patients Treated With Radical Prostatectomy. Prostate. 2017 Mar; 77(4):425-434.
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  6. Karami S, Han Y, Pande M, Cheng I, Rudd J, Pierce BL, Nutter EL, Schumacher FR, Kote-Jarai Z, Lindstrom S, Witte JS, Fang S, Han J, Kraft P, Hunter DJ, Song F, Hung RJ, McKay J, Gruber SB, Chanock SJ, Risch A, Shen H, Haiman CA, Boardman L, Ulrich CM, Casey G, Peters U, Amin Al Olama A, Berchuck A, Berndt SI, Bezieau S, Brennan P, Brenner H, Brinton L, Caporaso N, Chan AT, Chang-Claude J, Christiani DC, Cunningham JM, Easton D, Eeles RA, Eisen T, Gala M, Gallinger SJ, Gayther SA, Goode EL, Grönberg H, Henderson BE, Houlston R, Joshi AD, Küry S, Landi MT, Le Marchand L, Muir K, Newcomb PA, Permuth-Wey J, Pharoah P, Phelan C, Potter JD, Ramus SJ, Risch H, Schildkraut J, Slattery ML, Song H, Wentzensen N, White E, Wiklund F, Zanke BW, Sellers TA, Zheng W, Chatterjee N, Amos CI, Doherty JA. Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer. 2016 Dec 15; 139(12):2655-2670.
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  7. Marini NJ, Yang W, Asrani K, Witte JS, Rine J, Lammer EJ, Shaw GM. Sequence variation in folate pathway genes and risks of human cleft lip with or without cleft palate. Am J Med Genet A. 2016 Nov; 170(11):2777-2787.
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  8. 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 RHN, Stehouwer CDA, Logie L, Sutherland C, Klovins J, Pirags V, Hofman A, Stricker BH, Motsinger-Reif AA, Wagner MJ, Innocenti F, 't Hart LM, Holman RR, McCarthy MI, Hedderson MM, Palmer CNA, Florez JC, Giacomini KM, Pearson ER. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet. 2016 Sep; 48(9):1055-1059.
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  9. Brenner DR, Brennan P, Boffetta P, Amos CI, Spitz MR, Chen C, Goodman G, Heinrich J, Bickeböller H, Rosenberger A, Risch A, Muley T, McLaughlin JR, Benhamou S, Bouchardy C, Lewinger JP, Witte JS, Chen G, Bull S, Hung RJ. Erratum to: Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls. Hum Genet. 2016 Aug; 135(8):963.
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  10. 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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  11. Majumdar A, Haldar T, Witte JS. Determining Which Phenotypes Underlie a Pleiotropic Signal. Genet Epidemiol. 2016 07; 40(5):366-81.
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  12. 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 May 23; 20(1):151.
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  13. 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 07; 26(7):863-73.
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  14. 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 Apr 25; 7:11433.
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  15. 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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  16. 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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  17. 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, Conti DV, Albanes D, Berg C, Berndt SI, Campa D, Crawford ED, Diver WR, Gapstur SM, Gaziano JM, Giovannucci E, Hoover R, Hunter DJ, Johansson M, Kraft P, Le Marchand L, Lindström S, Navarro C, Overvad K, Riboli E, Siddiq A, Stevens VL, Trichopoulos D, Vineis P, Yeager M, Trynka G, Raychaudhuri S, Schumacher FR, Price AL, Freedman ML, Haiman CA, Pasaniuc B. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nat Commun. 2016 Apr 07; 7:10979.
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  18. 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 04 01; 76(7):1860-8.
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  19. 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 AJM, 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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  20. 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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