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. Li M, He Z, Tong X, Witte JS, Lu Q. Detecting Rare Mutations with Heterogeneous Effects Using a Family-Based Genetic Random Field Method. Genetics. 2018 Aug 13.
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  2. Zhang C, Wiemels JL, Hansen HM, Gonzalez-Maya J, Endicott AA, de Smith AJ, Smirnov IV, Witte JS, Morimoto LM, Metayer C, Walsh KM. Two HLA class II gene variants are independently associated with pediatric osteosarcoma risk. Cancer Epidemiol Biomarkers Prev. 2018 Jul 23.
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  3. Johnson DB, Bordeaux JM, Kim JY, Vaupel CA, Rimm DL, Ho TH, Joseph RW, Daud AI, Conry RM, Gaughan EM, Hernandez-Aya LF, Dimou A, Funchain P, Smithy JW, Witte JS, McKee SB, Ko J, Wrangle J, Dabbas B, Tangri S, Lameh J, Hall JM, Markowitz J, Balko JM, Dakappagari NK. Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of anti-PD-1 Therapies in Metastatic Melanoma. Clin Cancer Res. 2018 Jul 18.
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  4. Cario CL, Witte JS. Orchid: a novel management, annotation and machine learning framework for analyzing cancer mutations. Bioinformatics. 2018 Mar 15; 34(6):936-942.
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  5. Majumdar A, Haldar T, Bhattacharya S, Witte JS. An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations. PLoS Genet. 2018 Feb; 14(2):e1007139.
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  6. Asai Y, Eslami A, van Ginkel CD, Akhabir L, Wan M, Yin D, Ellis G, Ben-Shoshan M, Marenholz I, Martino D, Ferreira MA, Allen K, Mazer B, de Groot H, de Jong NW, Gerth van Wijk R, Dubois AEJ, Grosche S, Ashley S, Rüschendorf F, Kalb B, Beyer K, Nöthen MM, Lee YA, 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. A Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma. J Allergy Clin Immunol. 2018 Apr; 141(4):1513-1516.
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  7. 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. 2018 Jan; 27(1):75-85.
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  8. 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 Dec; 49(12):1752-1757.
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  9. 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. 2018 Mar; 141(3):991-1001.
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  10. 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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  11. 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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  12. 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 09; 13(9):e1006945.
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  13. Conti DV, Wang K, Sheng X, Bensen JT, Hazelett DJ, Cook MB, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs WB, Stanford JL, Zheng W, Sanderson M, John EM, Park JY, Xu J, Stevens VL, Berndt SI, Huff CD, Wang Z, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Sellers TA, Yamoah K, Murphy AB, Crawford DC, Gapstur SM, Bush WS, Aldrich MC, Cussenot O, Petrovics G, Cullen J, Neslund-Dudas C, Stern MC, Jarai ZK, Govindasami K, Chokkalingam AP, Hsing AW, Goodman PJ, Hoffmann T, Drake BF, Hu JJ, Clark PE, Van Den Eeden SK, Blanchet P, Fowke JH, Casey G, Hennis AJM, Han Y, Lubwama A, Thompson IM, Leach R, Easton DF, Schumacher F, Van den Berg DJ, Gundell SM, Stram A, Wan P, Xia L, Pooler LC, Mohler JL, Fontham ETH, Smith GJ, Taylor JA, Srivastava S, Eeles RA, Carpten J, Kibel AS, Multigner L, Parent ME, Menegaux F, Cancel-Tassin G, Klein EA, Brureau L, Stram DO, Watya S, Chanock SJ, Witte JS, Blot WJ, Henderson BE, Haiman CA. Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry. J Natl Cancer Inst. 2017 Aug 01; 109(8).
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  14. 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 Nov; 135(2):237-244.
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  15. 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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  16. 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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  17. 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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  18. 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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  19. 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 Aug; 15(8):1256-1264.
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  20. 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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