Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
Creators: name: Zhang, Yan Dora
name: Hurson, Amber N.
name: Zhang, Haoyu
name: Choudhury, Parichoy Pal
name: Hall, Per
name: Chang-Claude, Jenny
name: Campbell, Peter T.
name: Hoffmeister, Michael
name: Hsu, Li
name: Gruber, Stephen B.
name: Casey, Graham
name: De Vivo, Immaculata
name: Bishop, D. Timothy
name: Ward, Sarah V.
name: Bondy, Melissa L.
name: Wiencke, John K.
name: Melin, Beatrice
name: Wrensch, Margaret R.
name: McKay, James
name: Caporaso, Neil E.
name: Berndt, Sonja I.
name: Rothman, Nathaniel
name: Slager, Susan L.
name: Berchuck, Andrew
name: Sellers, Thomas A.
name: Pearce, Celeste L.
name: Goode, Ellen L.
name: Schildkraut, Joellen M.
name: Moysich, Kirsten B.
name: Petersen, Gloria M.
name: Risch, Harvey A.
name: Stolzenberg-Solomon, Rachel Z.
name: Wolpin, Brian M.
name: Li, Donghui
name: Haiman, Christopher A.
name: Kote-Jarai, Zsofia
name: Al Olama, Ali Amin
name: Purdue, Mark P.
name: Scelo, Ghislaine
name: Dalgaard, Marlene D.
name: Grotmol, Tom
name: McGlynn, Katherine A.
name: Turnbull, Clare
name: Chanock, Stephen J.
name: Chatterjee, Nilanjan
name: Garcia-Closas, Montserrat
name: Easton, Douglas F.
name: Milne, Roger L.
name: Simard, Jacques
name: Michailidou, Kyriaki
name: Dennis, Joe
name: Schmidt, Marjanka K.
name: Gharahkhani, Puya
name: Whiteman, David
name: Jenkins, Mark
name: Peters, Ulrike
name: Schmit, Stephanie L.
name: O’Mara, Tracy A.
name: Spurdle, Amanda B.
name: Thompson, Deborah J.
name: Tomlinson, Ian
name: Landi, Maria Teresa
name: Law, Matthew H.
name: Iles, Mark M.
name: Demenais, Florence
name: Kumar, Rajiv
name: MacGregor, Stuart
name: Bishop, David T.
name: Houlston, Richard
name: Barnholtz-Sloan, Jill
name: Kinnersley, Ben
name: Amos, Christopher I.
name: Hung, Rayjean J.
name: Brennan, Paul
name: Birmann, Brenda M.
name: Camp, Nicola J.
name: Kraft, Peter
name: Pharoah, Paul D. P.
name: Gayther, Simon A.
name: Amundadottir, Laufey T.
name: Jacobs, Eric J.
name: Klein, Alison P.
name: Eeles, Rosalind A.
name: Schumacher, Fredrick R.
name: Greene, Mark H.
name: Kanetsky, Peter A.
name: Nathanson, Katherine L.
name: Wiklund, Fredrik
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Article
/631/208/68
/692/699
/45
/45/43
article

description: 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.