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

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. Wu YH, Graff RE, Passarelli MN, Hoffman JD, Ziv E, Hoffmann TJ, Witte JS. Identification of pleiotropic cancer susceptibility variants from genome-wide association studies reveals functional characteristics. Cancer Epidemiol Biomarkers Prev. 2017 Nov 17.
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  2. Cario CL, Witte JS. orchid: a novel management, annotation, and machine learning framework for analyzing cancer mutations. Bioinformatics. 2017 Nov 02.
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  3. Ferreira MA, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, Helmer Q, Tillander A, Ullemar V, van Dongen J, Lu Y, Rüschendorf F, Esparza-Gordillo J, Medway CW, Mountjoy E, Burrows K, Hummel O, Grosche S, Brumpton BM, Witte JS, Hottenga JJ, Willemsen G, Zheng J, Rodríguez E, Hotze M, Franke A, Revez JA, Beesley J, Matheson MC, Dharmage SC, Bain LM, Fritsche LG, Gabrielsen ME, Balliu B. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet. 2017 Oct 30.
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  4. Asai Y, Eslami A, van Ginkel CD, Akhabir L, Wan M, Ellis G, Ben-Shoshan M, Martino D, Ferreira MA, Allen K, Mazer B, de Groot H, de Jong NW, Gerth van Wijk RN, Dubois AEJ, Chin R, Cheuk S, Hoffman J, Jorgensen E, Witte JS, Melles RB, Hong X, Wang X, Hui J, Musk AWB, Hunter M, James AL, Koppelman GH, Sandford AJ, Clarke AE, Daley D. Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy. J Allergy Clin Immunol. 2017 Oct 10.
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  5. McAllister K, Mechanic LE, Amos C, Aschard H, Blair IA, Chatterjee N, Conti D, Gauderman WJ, Hsu L, Hutter CM, Jankowska MM, Kerr J, Kraft P, Montgomery SB, Mukherjee B, Papanicolaou GJ, Patel CJ, Ritchie MD, Ritz BR, Thomas DC, Wei P, Witte JS. Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases. Am J Epidemiol. 2017 Oct 01; 186(7):753-761.
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  6. Gauderman WJ, Mukherjee B, Aschard H, Hsu L, Lewinger JP, Patel CJ, Witte JS, Amos C, Tai CG, Conti D, Torgerson DG, Lee S, Chatterjee N. Update on the State of the Science for Analytical Methods for Gene-Environment Interactions. Am J Epidemiol. 2017 Oct 01; 186(7):762-770.
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  7. Mechanic LE, Lindström S, Daily KM, Sieberts SK, Amos CI, Chen HS, Cox NJ, Dathe M, Feuer EJ, Guertin MJ, Hoffman J, Liu Y, Moore JH, Myers CL, Ritchie MD, Schildkraut J, Schumacher F, Witte JS, Wang W, Williams SM. Up For A Challenge (U4C): Stimulating innovation in breast cancer genetic epidemiology. PLoS Genet. 2017 Sep; 13(9):e1006945.
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  8. 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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  9. Ng MCY, Graff M, Lu Y, Justice AE, Mudgal P, Liu CT, Young K, Yanek LR, Feitosa MF, Wojczynski MK, Rand K, Brody JA, Cade BE, Dimitrov L, Duan Q, Guo X, Lange LA, Nalls MA, Okut H, Tajuddin SM, Tayo BO, Vedantam S, Bradfield JP, Chen G, Chen WM, Chesi A, Irvin MR, Padhukasahasram B, Smith JA, Zheng W, Allison MA, Ambrosone CB, Bandera EV, Bartz TM, Berndt SI, Bernstein L, Blot WJ, Bottinger EP, Carpten J, Chanock SJ, Chen YI, Conti DV, Cooper RS, Fornage M, Freedman BI, Garcia M, Goodman PJ, Hsu YH, Hu J, Huff CD, Ingles SA, John EM, Kittles R, Klein E, Li J, McKnight B, Nayak U, Nemesure B, Ogunniyi A, Olshan A, Press MF, Rohde R, Rybicki BA, Salako B, Sanderson M, Shao Y, Siscovick DS, Stanford JL, Stevens VL, Stram A, Strom SS, Vaidya D, Witte JS, Yao J, Zhu X, Ziegler RG, Zonderman AB, Adeyemo A, Ambs S, Cushman M, Faul JD, Hakonarson H, Levin AM, Nathanson KL, Ware EB, Weir DR, Zhao W, Zhi D. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium. PLoS Genet. 2017 Apr; 13(4):e1006719.
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  10. 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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  11. 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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  12. 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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  13. Graff RE, Möller S, Passarelli MN, Witte JS, Skytthe A, Christensen K, Tan Q, Adami HO, Czene K, Harris JR, Pukkala E, Kaprio J, Giovannucci EL, Mucci LA, Hjelmborg JB. Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer. Clin Gastroenterol Hepatol. 2017 Jan 24.
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  14. 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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  15. 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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  16. 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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  17. Rand KA, Song C, Dean E, Serie DJ, Curtin K, Sheng X, Hu D, Huff CA, Bernal-Mizrachi L, Tomasson MH, Ailawadhi S, Singhal S, Pawlish K, Peters ES, Bock CH, Stram A, Van Den Berg DJ, Edlund CK, Conti DV, Zimmerman T, Hwang AE, Huntsman S, Graff J, Nooka A, Kong Y, Pregja SL, Berndt SI, Blot WJ, Carpten J, Casey G, Chu L, Diver WR, Stevens VL, Lieber MR, Goodman PJ, Hennis AJ, Hsing AW, Mehta J, Kittles RA, Kolb S, Klein EA, Leske C, Murphy AB, Nemesure B, Neslund-Dudas C, Strom SS, Vij R, Rybicki BA, Stanford JL, Signorello LB, Witte JS, Ambrosone CB, Bhatti P, John EM, Bernstein L, Zheng W, Olshan AF, Hu JJ, Ziegler RG, Nyante SJ, Bandera EV, Birmann BM, Ingles SA, Press MF, Atanackovic D, Glenn MJ, Cannon-Albright LA, Jones B, Tricot G, Martin TG, Kumar SK, Wolf JL, Deming Halverson SL, Rothman N, Brooks-Wilson AR, Rajkumar SV, Kolonel LN, Chanock SJ, Slager SL, Severson RK, Janakiraman N, Terebelo HR, Brown EE, De Roos AJ, Mohrbacher AF, Colditz GA, Giles GG, Spinelli JJ, Chiu BC, Munshi NC, Anderson KC, Levy J, Zonder JA, Orlowski RZ, Lonial S, Camp NJ, Vachon CM, Ziv E, Stram DO, Hazelett DJ, Haiman CA, Cozen W. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci. Cancer Epidemiol Biomarkers Prev. 2016 Sep 1.
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  18. 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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  19. 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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  20. 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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