Research Summary

The Witte Lab is a computational and epidemiological research group investigating the genetic and environmental contributions to disease risk and progression. We develop and apply novel genetic epidemiological methods to decipher the mechanisms underlying complex diseases. In particular, we focus on: 1) Pleiotropy: assessing the shared genetic basis across cancers and other diseases; 2) Risk Modeling: evaluating disease risk with polygenic risk scores (PRS) and hierarchical models; 3) Prostate Cancer: finding genetic risk factors, improving screening, and reducing disparities; and 4) Liquid Biopsy: detecting tumor mutations and determining response to immunotherapy.

Research Funding

  • December 1, 2004 - June 30, 2025 - Training in the Molecular & Genetic Epidemiology of Cancer, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: T32CA112355
  • April 1, 2020 - March 31, 2024 - Precision Prostate Cancer Screening with Genetically Adjusted Prostate-Specific Antigen Levels, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA241410
  • August 1, 2016 - July 31, 2020 - Genome-wide Pleiotropy Scan across Multiple Cancers, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA201358
  • December 1, 2004 - August 31, 2019 - Training in Molecular& Genetic Epidemiology of Cancer, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R25CA112355

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

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
  • 2010
    Directors Invited Lecture, NHGRI / NIH
  • 2011
    Stephen B. Hulley Award for Excellence In Teaching, UCSF Training in Clinical Research
  • 2016
    Up for a Challenge Grand Prize, National Cancer Institute
  • 2017
    Robert Millikan Symposium Memorial Lecture, Univ North Carolina Lineberger Comprehensive Cancer Center
  • 2018
    Leadership Award, International Genetic Epidemiology Society

Selected Publications

  1. Desai AS, Sagar V, Lysy B, Weiner AB, Ko OS, Driscoll C, Rodriguez Y, Vatapalli R, Unno K, Han H, Cohen JE, Vo AX, Pham M, Shin M, Jain-Poster K, Ross J, Morency EG, Meyers TJ, Witte JS, Wu J, Abdulkadir SA, Kundu SD. Correction: Inflammatory bowel disease induces inflammatory and preneoplastic changes in the prostate. Prostate Cancer Prostatic Dis. 2021 Jun 22.  View on PubMed
  2. Li M, Lyu C, Huang M, Do C, Tycko B, Lupo PJ, MacLeod SL, Randolph CE, Liu N, Witte JS, Hobbs CA. Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease. BMC Genom Data. 2021 Jun 10; 22(1):20.  View on PubMed
  3. Desai AS, Sagar V, Lysy B, Weiner AB, Ko OS, Driscoll C, Rodriguez Y, Vatapalli R, Unno K, Han H, Cohen JE, Vo AX, Pham M, Shin M, Jain-Poster K, Ross J, Morency EG, Meyers TJ, Witte JS, Wu J, Abdulkadir SA, Kundu SD. Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate. Prostate Cancer Prostatic Dis. 2021 May 25.  View on PubMed
  4. Chen E, Cario CL, Leong L, Lopez K, Márquez CP, Li PS, Oropeza E, Tenggara I, Cowan J, Simko JP, Kageyama R, Wells DK, Chan JM, Friedlander T, Aggarwal R, Paris PL, Feng F, Carroll PR, Witte JS. Cell-Free DNA Detection of Tumor Mutations in Heterogeneous, Localized Prostate Cancer Via Targeted, Multiregion Sequencing. JCO Precis Oncol. 2021; 5.  View on PubMed
  5. Gaylis FD, Cooperberg MR, Chen RC, Malin J, Loeb S, Witte JS, Carroll PR, Cohen ES, Dato PE, Lin DW, Zheng Y, Seibert TM, Setzler C, Wilt W, Gomez SL, Chan JML, Catalona WJ. Defining Quality Metrics for Active Surveillance: The Michigan Urological Surgery Improvement Collaborative Experience. Letter. J Urol. 2021 Apr 05; 101097JU0000000000001781.  View on PubMed
  6. Graff M, Justice AE, Young KL, Marouli E, Zhang X, Fine RS, Lim E, Buchanan V, Rand K, Feitosa MF, Wojczynski MK, Yanek LR, Shao Y, Rohde R, Adeyemo AA, Aldrich MC, Allison MA, Ambrosone CB, Ambs S, Amos C, Arnett DK, Atwood L, Bandera EV, Bartz T, Becker DM, Berndt SI, Bernstein L, Bielak LF, Blot WJ, Bottinger EP, Bowden DW, Bradfield JP, Brody JA, Broeckel U, Burke G, Cade BE, Cai Q, Caporaso N, Carlson C, Carpten J, Casey G, Chanock SJ, Chen G, Chen M, Chen YI, Chen WM, Chesi A, Chiang CWK, Chu L, Coetzee GA, Conti DV, Cooper RS, Cushman M, Demerath E, Deming SL, Dimitrov L, Ding J, Diver WR, Duan Q, Evans MK, Falusi AG, Faul JD, Fornage M, Fox C, Freedman BI, Garcia M, Gillanders EM, Goodman P, Gottesman O, Grant SFA, Guo X, Hakonarson H, Haritunians T, Harris TB, Harris CC, Henderson BE, Hennis A, Hernandez DG, Hirschhorn JN, McNeill LH, Howard TD, Howard B, Hsing AW, Hsu YH, Hu JJ, Huff CD, Huo D, Ingles SA, Irvin MR, John EM, Johnson KC, Jordan JM, Kabagambe EK, Kang SJ, Kardia SL, Keating BJ, Kittles RA, Klein EA, Kolb S, Kolonel LN, Kooperberg C, Kuller L, Kutlar A, Lange L, Langefeld CD, Le Marchand L, Leonard H, Lettre G, Levin AM, Li Y, Li J, Liu Y, Liu Y, Liu S, Lohman K, Lotay V, Lu Y, Maixner W, Manson JE, McKnight B, Meng Y, Monda KL, Monroe K, Moore JH, Mosley TH, Mudgal P, Murphy AB, Nadukuru R, Nalls MA, Nathanson KL, Nayak U, N'Diaye A, Nemesure B, Neslund-Dudas C, Neuhouser ML, Nyante S, Ochs-Balcom H, Ogundiran TO, Ogunniyi A, Ojengbede O, Okut H, Olopade OI, Olshan A, Padhukasahasram B, Palmer J, Palmer CD, Palmer ND, Papanicolaou G, Patel SR, Pettaway CA, Peyser PA, Press MF, Rao DC, Rasmussen-Torvik LJ, Redline S, Reiner AP, Rhie SK, Rodriguez-Gil JL, Rotimi CN, Rotter JI, Ruiz-Narvaez EA, Rybicki BA, Salako B, Sale MM, Sanderson M, Schadt E, Schreiner PJ, Schurmann C, Schwartz AG, Shriner DA, Signorello LB, Singleton AB, Siscovick DS, Smith JA, Smith S, Speliotes E, Spitz M, Stanford JL, Stevens VL, Stram A, Strom SS, Sucheston L, Sun YV, Tajuddin SM, Taylor H, Taylor K, Tayo BO, Thun MJ, Tucker MA, Vaidya D, Van Den Berg DJ, Vedantam S, Vitolins M, Wang Z, Ware EB, Wassertheil-Smoller S, Weir DR, Wiencke JK, Williams SM, Williams LK, Wilson JG, Witte JS, Wrensch M, Wu X, Yao J, Zakai N, Zanetti K, Zemel BS, Zhao W, Zhao JH, Zheng W, Zhi D, Zhou J, Zhu X, Ziegler RG, Zmuda J, Zonderman AB, Psaty BM, Borecki IB, Cupples LA, Liu CT, Haiman CA, Loos R, Ng MCY, North KE. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry. Am J Hum Genet. 2021 04 01; 108(4):564-582.  View on PubMed
  7. Chen E, Cario CL, Leong L, Lopez K, Márquez CP, Chu C, Li PS, Oropeza E, Tenggara I, Cowan J, Simko JP, Chan JM, Friedlander T, Wyatt AW, Aggarwal R, Paris PL, Carroll PR, Feng F, Witte JS. Cell-free DNA concentration and fragment size as a biomarker for prostate cancer. Sci Rep. 2021 Mar 03; 11(1):5040.  View on PubMed
  8. Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, Schumacher FR, Olama AAA, Benlloch S, Dadaev T, Brook MN, Sahimi A, Hoffmann TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Muir K, Lophatananon A, Wan P, Le Marchand L, Wilkens LR, Stevens VL, Gapstur SM, Carter BD, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder MA, Iversen P, Batra J, Chambers S, Moya L, Horvath L, Clements JA, Tilley W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordström T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein SJ, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Geybels MS, Koutros S, Freeman LEB, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Burnet N, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Fontham ETH, Mohler J, Taylor JA, Kogevinas M, Llorca J, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Weaver B, Brenner H, Cuk K, Holleczek B, Saum KU, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen JC, Petrovics G, Casey G, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Varma R, McKean-Cowdin R, Torres M, Mancuso N, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Nakagawa H, Witte JS, Eeles RA, Kote-Jarai Z, Haiman CA. Publisher Correction: Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021 Mar; 53(3):413.  View on PubMed
  9. Graff RE, Cavazos TB, Thai KK, Kachuri L, Rashkin SR, Hoffman JD, Alexeeff SE, Blatchins M, Meyers TJ, Leong L, Tai CG, Emami NC, Corley DA, Kushi LH, Ziv E, Van Den Eeden SK, Jorgenson E, Hoffmann TJ, Habel LA, Witte JS, Sakoda LC. Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts. Nat Commun. 2021 02 12; 12(1):970.  View on PubMed
  10. Majumdar A, Burch KS, Haldar T, Sankararaman S, Pasaniuc B, Gauderman WJ, Witte JS. A two-step approach to testing overall effect of gene-environment interaction for multiple phenotypes. Bioinformatics. 2021 Jan 16.  View on PubMed
  11. Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, Schumacher FR, Olama AAA, Benlloch S, Dadaev T, Brook MN, Sahimi A, Hoffmann TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Muir K, Lophatananon A, Wan P, Le Marchand L, Wilkens LR, Stevens VL, Gapstur SM, Carter BD, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder MA, Iversen P, Batra J, Chambers S, Moya L, Horvath L, Clements JA, Tilley W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordström T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein SJ, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Geybels MS, Koutros S, Freeman LEB, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Burnet N, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Fontham ETH, Mohler J, Taylor JA, Kogevinas M, Llorca J, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Weaver B, Brenner H, Cuk K, Holleczek B, Saum KU, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen JC, Petrovics G, Casey G, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Varma R, McKean-Cowdin R, Torres M, Mancuso N, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Nakagawa H, Witte JS, Eeles RA, Kote-Jarai Z, Haiman CA. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021 01; 53(1):65-75.  View on PubMed
  12. Emami NC, Cavazos TB, Rashkin SR, Cario CL, Graff RE, Tai CG, Mefford JA, Kachuri L, Wan E, Wong S, Aaronson D, Presti J, Habel LA, Shan J, Ranatunga DK, Chao CR, Ghai NR, Jorgenson E, Sakoda LC, Kvale MN, Kwok PY, Schaefer C, Risch N, Hoffmann TJ, Van Den Eeden SK, Witte JS. A Large-Scale Association Study Detects Novel Rare Variants, Risk Genes, Functional Elements, and Polygenic Architecture of Prostate Cancer Susceptibility. Cancer Res. 2021 04 01; 81(7):1695-1703.  View on PubMed
  13. Cavazos TB, Witte JS. Inclusion of variants discovered from diverse populations improves polygenic risk score transferability. HGG Adv. 2021 Jan 14; 2(1).  View on PubMed
  14. Kachuri L, Graff RE, Smith-Byrne K, Meyers TJ, Rashkin SR, Ziv E, Witte JS, Johansson M. Pan-cancer analysis demonstrates that integrating polygenic risk scores with modifiable risk factors improves risk prediction. Nat Commun. 2020 11 27; 11(1):6084.  View on PubMed
  15. Ospina-Romero M, Glymour MM, Hayes-Larson E, Mayeda ER, Graff RE, Brenowitz WD, Ackley SF, Witte JS, Kobayashi LC. Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 11 02; 3(11):e2025515.  View on PubMed
  16. Kachuri L, Francis SS, Morrison ML, Wendt GA, Bossé Y, Cavazos TB, Rashkin SR, Ziv E, Witte JS. The landscape of host genetic factors involved in immune response to common viral infections. Genome Med. 2020 10 27; 12(1):93.  View on PubMed
  17. Rashkin SR, Graff RE, Kachuri L, Thai KK, Alexeeff SE, Blatchins MA, Cavazos TB, Corley DA, Emami NC, Hoffman JD, Jorgenson E, Kushi LH, Meyers TJ, Van Den Eeden SK, Ziv E, Habel LA, Hoffmann TJ, Sakoda LC, Witte JS. Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts. Nat Commun. 2020 09 04; 11(1):4423.  View on PubMed
  18. Hayes-Larson E, Ackley SF, Zimmerman SC, Ospina-Romero M, Glymour MM, Graff RE, Witte JS, Kobayashi LC, Mayeda ER. The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association. Alzheimers Dement. 2020 12; 16(12):1696-1703.  View on PubMed
  19. Cario CL, Chen E, Leong L, Emami NC, Lopez K, Tenggara I, Simko JP, Friedlander TW, Li PS, Paris PL, Carroll PR, Witte JS. A machine learning approach to optimizing cell-free DNA sequencing panels: with an application to prostate cancer. BMC Cancer. 2020 Aug 28; 20(1):820.  View on PubMed
  20. Carmichael SL, Ma C, Witte JS, Yang W, Rasmussen SA, Brunelli L, Nestoridi E, Shaw GM, Feldkamp ML, National Birth Defects Prevention Study . Congenital diaphragmatic hernia and maternal dietary nutrient pathways and diet quality. Birth Defects Res. 2020 11; 112(18):1475-1483.  View on PubMed

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