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Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

Author

Listed:
  • Yan Dora Zhang

    (The University of Hong Kong
    The University of Hong Kong)

  • Amber N. Hurson

    (National Cancer Institute
    University of North Carolina at Chapel Hill)

  • Haoyu Zhang

    (National Cancer Institute
    Johns Hopkins University)

  • Parichoy Pal Choudhury

    (National Cancer Institute)

  • Douglas F. Easton

    (University of Cambridge
    University of Cambridge)

  • Roger L. Milne

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Jacques Simard

    (Centre Hospitalier Universitaire de Québec–Université Laval Research Center)

  • Per Hall

    (Karolinska Institutet
    Södersjukhuset)

  • Kyriaki Michailidou

    (University of Cambridge
    The Cyprus Institute of Neurology & Genetics)

  • Joe Dennis

    (University of Cambridge)

  • Marjanka K. Schmidt

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute)

  • David Whiteman

    (QIMR Berghofer Medical Research Institute)

  • Peter T. Campbell

    (American Cancer Society)

  • Michael Hoffmeister

    (German Cancer Research Center (DKFZ))

  • Mark Jenkins

    (The University of Melbourne)

  • Ulrike Peters

    (Fred Hutchinson Cancer Research Center)

  • Li Hsu

    (Fred Hutchinson Cancer Research Center)

  • Stephen B. Gruber

    (University of Southern California)

  • Graham Casey

    (University of Virginia)

  • Stephanie L. Schmit

    (H. Lee Moffitt Cancer Center and Research Institution)

  • Tracy A. O’Mara

    (QIMR Berghofer Medical Research Institute)

  • Amanda B. Spurdle

    (QIMR Berghofer Medical Research Institute)

  • Deborah J. Thompson

    (University of Cambridge)

  • Ian Tomlinson

    (University of Birmingham
    University of Oxford)

  • Immaculata De Vivo

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health)

  • Maria Teresa Landi

    (National Cancer Institute)

  • Matthew H. Law

    (QIMR Berghofer Medical Research Institute)

  • Mark M. Iles

    (University of Leeds)

  • Florence Demenais

    (Université de Paris, UMRS-1124, Institut National de la Santé et de la Recherche Médicale (INSERM))

  • Rajiv Kumar

    (German Cancer Research Center (DKFZ))

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute)

  • D. Timothy Bishop

    (University of Leeds)

  • Sarah V. Ward

    (The University of Western Australia)

  • Melissa L. Bondy

    (Baylor College of Medicine)

  • Richard Houlston

    (The Institute of Cancer Research)

  • John K. Wiencke

    (University of California, San Francisco)

  • Beatrice Melin

    (Umeå University)

  • Jill Barnholtz-Sloan

    (Case Western Reserve University School of Medicine)

  • Ben Kinnersley

    (The Institute of Cancer Research)

  • Margaret R. Wrensch

    (University of California, San Francisco)

  • Christopher I. Amos

    (Baylor College of Medicine)

  • Rayjean J. Hung

    (Sinai Health System)

  • Paul Brennan

    (World Health Organization)

  • James McKay

    (World Health Organization)

  • Neil E. Caporaso

    (National Cancer Institute)

  • Sonja I. Berndt

    (National Cancer Institute)

  • Brenda M. Birmann

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Nicola J. Camp

    (University of Utah School of Medicine)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health)

  • Nathaniel Rothman

    (National Cancer Institute)

  • Susan L. Slager

    (Mayo Clinic)

  • Andrew Berchuck

    (Duke University Medical Center)

  • Paul D. P. Pharoah

    (University of Cambridge
    University of Cambridge)

  • Thomas A. Sellers

    (H. Lee Moffitt Cancer Center and Research Institution)

  • Simon A. Gayther

    (Cedars-Sinai Medical Center)

  • Celeste L. Pearce

    (University of Southern California
    University of Michigan School of Public Health)

  • Ellen L. Goode

    (Mayo Clinic)

  • Joellen M. Schildkraut

    (Emory University)

  • Kirsten B. Moysich

    (Roswell Park Cancer Institute)

  • Laufey T. Amundadottir

    (National Cancer Institute, National Institutes of Health)

  • Eric J. Jacobs

    (American Cancer Society)

  • Alison P. Klein

    (Johns Hopkins School of Medicine)

  • Gloria M. Petersen

    (Mayo Clinic)

  • Harvey A. Risch

    (Yale School of Medicine)

  • Rachel Z. Stolzenberg-Solomon

    (National Cancer Institute)

  • Brian M. Wolpin

    (Dana-Farber Cancer Institute)

  • Donghui Li

    (The University of Texas MD Anderson Cancer Center)

  • Rosalind A. Eeles

    (Division of Genetics and Epidemiology, The Institute of Cancer Research)

  • Christopher A. Haiman

    (University of Southern California)

  • Zsofia Kote-Jarai

    (Division of Genetics and Epidemiology, The Institute of Cancer Research)

  • Fredrick R. Schumacher

    (Case Western Reserve University School of Medicine)

  • Ali Amin Al Olama

    (University of Cambridge
    University of Cambridge)

  • Mark P. Purdue

    (National Cancer Institute)

  • Ghislaine Scelo

    (World Health Organization)

  • Marlene D. Dalgaard

    (Copenhagen University Hospital (Rigshospitalet)
    Technical University of Denmark)

  • Mark H. Greene

    (National Cancer Institute)

  • Tom Grotmol

    (Cancer Registry of Norway)

  • Peter A. Kanetsky

    (H. Lee Moffitt Cancer Center and Research Institution)

  • Katherine A. McGlynn

    (National Cancer Institute)

  • Katherine L. Nathanson

    (University of Pennsylvania)

  • Clare Turnbull

    (The Institute of Cancer Research)

  • Fredrik Wiklund

    (Karolinska Institutet)

  • Stephen J. Chanock

    (National Cancer Institute)

  • Nilanjan Chatterjee

    (Johns Hopkins University
    Johns Hopkins School of Medicine)

  • Montserrat Garcia-Closas

    (National Cancer Institute)

Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Suggested Citation

  • Yan Dora Zhang & Amber N. Hurson & Haoyu Zhang & Parichoy Pal Choudhury & Douglas F. Easton & Roger L. Milne & Jacques Simard & Per Hall & Kyriaki Michailidou & Joe Dennis & Marjanka K. Schmidt & Jenn, 2020. "Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16483-3
    DOI: 10.1038/s41467-020-16483-3
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    Cited by:

    1. Jianxin Shi & Kouya Shiraishi & Jiyeon Choi & Keitaro Matsuo & Tzu-Yu Chen & Juncheng Dai & Rayjean J. Hung & Kexin Chen & Xiao-Ou Shu & Young Tae Kim & Maria Teresa Landi & Dongxin Lin & Wei Zheng & , 2023. "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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