Journal article

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

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, Jenny Chang-Claude, Puya Gharahkhani, David Whiteman, Peter T Campbell, Michael Hoffmeister, Mark Jenkins, Ulrike Peters, Li Hsu, Stephen B Gruber Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020


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 perce..

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Awarded by RO1 grant from NHGRI

Funding Acknowledgements

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