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Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts

Author

Listed:
  • Sara R. Rashkin

    (University of California, San Francisco)

  • Rebecca E. Graff

    (University of California, San Francisco
    Kaiser Permanente Northern California)

  • Linda Kachuri

    (University of California, San Francisco)

  • Khanh K. Thai

    (Kaiser Permanente Northern California)

  • Stacey E. Alexeeff

    (Kaiser Permanente Northern California)

  • Maruta A. Blatchins

    (Kaiser Permanente Northern California)

  • Taylor B. Cavazos

    (University of California, San Francisco
    University of California, San Francisco)

  • Douglas A. Corley

    (Kaiser Permanente Northern California)

  • Nima C. Emami

    (University of California, San Francisco
    University of California, San Francisco)

  • Joshua D. Hoffman

    (University of California, San Francisco)

  • Eric Jorgenson

    (Kaiser Permanente Northern California)

  • Lawrence H. Kushi

    (Kaiser Permanente Northern California)

  • Travis J. Meyers

    (University of California, San Francisco)

  • Stephen K. Eeden

    (Kaiser Permanente Northern California
    University of California, San Francisco)

  • Elad Ziv

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Laurel A. Habel

    (Kaiser Permanente Northern California)

  • Thomas J. Hoffmann

    (University of California, San Francisco
    Kaiser Permanente Northern California
    University of California, San Francisco)

  • Lori C. Sakoda

    (Kaiser Permanente Northern California)

  • John S. Witte

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

Abstract

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

Suggested Citation

  • Sara R. Rashkin & Rebecca E. Graff & Linda Kachuri & Khanh K. Thai & Stacey E. Alexeeff & Maruta A. Blatchins & Taylor B. Cavazos & Douglas A. Corley & Nima C. Emami & Joshua D. Hoffman & Eric Jorgens, 2020. "Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18246-6
    DOI: 10.1038/s41467-020-18246-6
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    Cited by:

    1. Hui Chen & Zeyang Wang & Lihai Gong & Qixuan Wang & Wenyan Chen & Jia Wang & Xuelian Ma & Ruofan Ding & Xing Li & Xudong Zou & Mireya Plass & Cheng Lian & Ting Ni & Gong-Hong Wei & Wei Li & Lin Deng &, 2024. "A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Go Sato & Yuya Shirai & Shinichi Namba & Ryuya Edahiro & Kyuto Sonehara & Tsuyoshi Hata & Mamoru Uemura & Koichi Matsuda & Yuichiro Doki & Hidetoshi Eguchi & Yukinori Okada, 2023. "Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Derek W. Brown & Weiyin Zhou & Youjin Wang & Kristine Jones & Wen Luo & Casey Dagnall & Kedest Teshome & Alyssa Klein & Tongwu Zhang & Shu-Hong Lin & Olivia W. Lee & Sairah Khan & Jacqueline B. Vo & A, 2022. "Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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