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