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Author Notes:

Correspondence: Nilanjan Chatterjee, nchatte2@jhu.edu

Author contributions: N.C. and M.G.-C. conceived the project. Y.Z. and A.W. performed main analyses. Y.Z., N.C., and M.G.-C. wrote the first draft of the manuscript. BCAC, BEACON, CCFR, CORECT, ECAC, GECCO, GenoMEL, GICC, ILCCO, Integral, InterLymph, OCAC, Oral Cancer GWAS, PANC4, PanScan, PRACTICAL, Renal Cancer GWAS, and TECAC contributed data.

P.P.C., R.L.M., M.K.S., M.J., U.P., L.H., S.L. Schmit., T.A.O., A.B.S., D.J.T., M.H.L., M.M.I., F.D., S.M., S.V.W., M.R.W., C.I.A., S.I.B., B.M.B., N.J.C., P.D.P.P., T.A.S., L.T.A., E.J.J., H.A.R., R.Z.S.-S., M.P.P., M.H.G., K.A.M., and S.J.C. commented on earlier drafts of the manuscript.

H.Z., D.F.E., J.S., P.H., K.M., J.D., J.C.-C., P.G., D.W., P.T.C., M.H., S.B.G., G.C., I.T., I.D.V., M.T.L., R.K., D.T.B., M.L.B., R.H., J.K.W., B.M., J.B.-S., B.K., R.J.H., P.B., J.M., N.E.C., P.K., N.R., S.L. Slager., A.B., S.A.G., C.L.P., E.L.G., J.M.S., K.B.M., A.P.K., G.M.P., B.M.W., D.L., R.A.E., C.A.H., Z.K.-J., F.R.S., A.A.A.O., G.S., M.D.D., T.G., P.A.K., K.L.N., C.T., and F.W. reviewed the manuscript.

All authors reviewed and approved the final draft of the manuscript.

Disclosures: The authors declare no competing interests.

Subjects:

Research Funding:

The research was supported by an RO1 grant from NHGRI (1 R01 HG010480-01) and the intramural program of the National Cancer Institute.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • Genome-wide association
  • LD score regression
  • Susceptibility loci
  • Breast cancer
  • Genetic susceptibility
  • Heritability
  • Identification
  • Metaanalysis
  • Inference

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

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Journal Title:

Nature Communications

Volume:

Volume 11, Number 1

Publisher:

, Pages 3353-3353

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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