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

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Zhang, YD (author)

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

Article/chapterEnglish2020

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2020-07-03
Springer Science and Business Media LLC,2020

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LIBRIS-ID:oai:prod.swepub.kib.ki.se:144129576
http://kipublications.ki.se/Default.aspx?queryparsed=id:144129576URI
https://doi.org/10.1038/s41467-020-16483-3DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-173720URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

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Hurson, AN (author)
Zhang, HY (author)
Choudhury, PP (author)
Easton, DF (author)
Milne, RL (author)
Simard, J (author)
Hall, PKarolinska Institutet (author)
Michailidou, K (author)
Dennis, J (author)
Schmidt, MK (author)
Chang-Claude, J (author)
Gharahkhani, P (author)
Whiteman, D (author)
Campbell, PT (author)
Hoffmeister, M (author)
Jenkins, M (author)
Peters, U (author)
Hsu, L (author)
Gruber, SB (author)
Casey, G (author)
Schmit, SL (author)
O'Mara, TA (author)
Spurdle, AB (author)
Thompson, DJ (author)
Tomlinson, I (author)
De Vivo, I (author)
Landi, MT (author)
Law, MH (author)
Iles, MM (author)
Demenais, F (author)
Kumar, R (author)
MacGregor, S (author)
Bishop, DT (author)
Ward, SV (author)
Bondy, ML (author)
Houlston, R (author)
Wiencke, JK (author)
Melin, Beatrice S.Umeå universitet,Onkologi,Glioma International Case-Control Study (GICC)(Swepub:umu)bema0010 (author)
Barnholtz-Sloan, J (author)
Kinnersley, B (author)
Wrensch, MR (author)
Amos, CI (author)
Hung, RJ (author)
Brennan, P (author)
McKay, J (author)
Caporaso, NE (author)
Berndt, SI (author)
Birmann, BM (author)
Camp, NJ (author)
Kraft, P (author)
Rothman, N (author)
Slager, SL (author)
Berchuck, A (author)
Pharoah, PDP (author)
Sellers, TA (author)
Gayther, SA (author)
Pearce, CL (author)
Goode, EL (author)
Schildkraut, JM (author)
Moysich, KB (author)
Amundadottir, LT (author)
Jacobs, EJ (author)
Klein, AP (author)
Petersen, GM (author)
Risch, HA (author)
Stolzenberg-Solomon, RZ (author)
Wolpin, BM (author)
Li, DH (author)
Eeles, RA (author)
Haiman, CA (author)
Kote-Jarai, Z (author)
Schumacher, FR (author)
Al Olama, AA (author)
Purdue, MP (author)
Scelo, G (author)
Dalgaard, MD (author)
Greene, MH (author)
Grotmol, T (author)
Kanetsky, PA (author)
McGlynn, KA (author)
Nathanson, KL (author)
Turnbull, C (author)
Wiklund, FKarolinska Institutet (author)
Chanock, SJ (author)
Chatterjee, N (author)
Garcia-Closas, M (author)
Karolinska InstitutetOnkologi (creator_code:org_t)

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In:Nature communications: Springer Science and Business Media LLC11:1, s. 3353-2041-1723

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By the author/editor: Zhang, YD; Hurson, AN; Zhang, HY; Choudhury, PP; Easton, DF; Milne, RL; show more...; Simard, J; Hall, P; Michailidou, K; Dennis, J; Schmidt, MK; Chang-Claude, J; Gharahkhani, P; Whiteman, D; Campbell, PT; Hoffmeister, M; Jenkins, M; Peters, U; Hsu, L; Gruber, SB; Casey, G; Schmit, SL; O'Mara, TA; Spurdle, AB; Thompson, DJ; Tomlinson, I; De Vivo, I; Landi, MT; Law, MH; Iles, MM; Demenais, F; Kumar, R; MacGregor, S; Bishop, DT; Ward, SV; Bondy, ML; Houlston, R; Wiencke, JK; Melin, Beatrice ...; Barnholtz-Sloan, ...; Kinnersley, B; Wrensch, MR; Amos, CI; Hung, RJ; Brennan, P; McKay, J; Caporaso, NE; Berndt, SI; Birmann, BM; Camp, NJ; Kraft, P; Rothman, N; Slager, SL; Berchuck, A; Pharoah, PDP; Sellers, TA; Gayther, SA; Pearce, CL; Goode, EL; Schildkraut, JM; Moysich, KB; Amundadottir, LT; Jacobs, EJ; Klein, AP; Petersen, GM; Risch, HA; Stolzenberg-Solo ...; Wolpin, BM; Li, DH; Eeles, RA; Haiman, CA; Kote-Jarai, Z; Schumacher, FR; Al Olama, AA; Purdue, MP; Scelo, G; Dalgaard, MD; Greene, MH; Grotmol, T; Kanetsky, PA; McGlynn, KA; Nathanson, KL; Turnbull, C; Wiklund, F; Chanock, SJ; Chatterjee, N; Garcia-Closas, M; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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By the university: Karolinska Institutet; Umeå University

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