Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independ...

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Published inNature genetics Vol. 53; no. 1; pp. 65 - 75
Main Authors Schumacher, Fredrick R, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Wan, Peggy, Stevens, Victoria L, Carter, Brian D, Schleutker, Johanna, Auvinen, Anssi, MacInnis, Robert J, Lubiński, Jan, Donovan, Jenny L, Hamdy, Freddie C, Nordestgaard, Børge G, Batra, Jyotsna, Tilley, Wayne, Risbridger, Gail P, Eklund, Martin, Lin, Hui-Yi, Giovannucci, Edward, Kraft, Peter, Turman, Constance, Fleshner, Neil E, Parent, Marie-Élise, Ostrander, Elaine A, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Lu, Yong-Jie, Feng, Ninghan, Wu, Yudong, Schaid, Daniel J, West, Catharine M L, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Kibel, Adam S, Truong, Thérèse, Grindedal, Eli Marie, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Fachal, Laura, Kerns, Sarah L, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Kogevinas, Manolis, Llorca, Javier, Cannon-Albright, Lisa, Huff, Chad D, Strom, Sara S, Kaneva, Radka, Leach, Robin J, Holleczek, Bernd, Klein, Eric A, Hsing, Ann W, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm J M, Carpten, John, Pandha, Hardev, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Kulis, Tomislav, Gago-Dominguez, Manuela, Martinez, Maria Elena, Larkin, Samantha, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Cullen, Jennifer C, Roobol, Monique J, Jenster, Guido, Varma, Rohit, McKean-Cowdin, Roberta, Berndt, Sonja I, Chanock, Stephen J, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Kote-Jarai, Zsofia
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.01.2021
Subjects
Age
Cancer och onkologi
Confidence intervals
Consortia
Estimates
Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
Gene loci
Genealogy
Genetic aspects
Genetic Loci
Genetic Predisposition to Disease
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Health aspects
Health risk assessment
Health risks
Hispanic Americans
Humans
Hälsovetenskap
Identification and classification
Klinisk medicin
Life Sciences
Male
Medical diagnosis
Medicin och hälsovetenskap
Medicinsk genetik
Medicinska och farmaceutiska grundvetenskaper
Meta-analysis
Middle Aged
Molecular Sequence Annotation
Neoplasm Invasiveness
Odds Ratio
Prostate cancer
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - genetics
Quantitative trait loci
Racial Groups - genetics
Risk
Risk Factors
United States
United Kingdom > UK
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Summary:Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
Bibliography:PMCID: PMC8148035
Drs. Conti, Eeles, Kote-Jarai and Haiman contributed equally to this article.
Drs. Conti and Darst are co-first authors
DVC, RAE, ZK-J and CAH contributed to study conception, and DVC, BFD, RAE, ZK-J and CAH contributed to interpretation and wrote the manuscript. EJS performed a literature search. MB, TD, SB and XS provided data management and bioinformatics support. DVC, LM, BD, EJS, TD, ZK-J and CAH contributed to data analysis and interpretation. All authors contributed data to the study, revised, critically reviewed and approved the final version of the manuscript: DVC, BDF, LCM, EJS, XS, AC, FRS, AAAO, SB, TD, MNB, AS, TJH, AT, KoMa, YM, MF, KeMu, ArLo, PW, LLM, LRW, VLS, SMG, BDC, JS, TLJT, CsSi, AA, GGG, MeCS, RJM, CC, DW, JaLu, DEN, JLD, FCH, RMM, BGN, SFN, MW, SEB, MAR, PI, JB, SC, LeMo, LH, JAC, WT, GPR, HG, MA, RS, ME, TN, NP, AMD, MGh, RCT, TJK, ER, JYP, TAS, H-YL, DA, SJW, LAM, EG, SaLi, PK, DJH, KLP, CT, CMT, PJG, IAM, RJH, NEF, AF, M-ÉP, JLS, EAO, MSG, SK, LEBF, MeSt, AW, NH, GLA, RNH, MJM, KDS, MB, WJB, WZ, EDY, JEM, Y-JL, H-WZ, NF, XM, YW, S-CZ, ZS, SNT, SKM, DJS, CMLW, NB, GB, CM, TS, ML, ASK, BFD, OC, GC-T, FM, TT, YAK, EMJ, EMG, LoMa, K-TK, SAI, MaCS, AV, AG-C, LF, BSR, SLK, HO, MRT, PP, AB, SW, AlLu, JTB, ETHF, JM, JAT, MK, JaLl, GC-V, LC-A, CCT, CDH, SSS, LuMu, PB, LB, RK, ChSl, VM, RJL, BW, HB, KC, BH, K-US, EAK, AWH, RAK, ABM, CJL, JK, SLN, LS, YCD, WBI, BN, AJMH, JC, HP, AM, KDR, GDM, PO, JX, AR, JaLi, S-HT, LFN, DWL, JHF, CN-D, BAR, MaG, DL, TK, NU, SaSi, MP, FC, SJ, TVB, MG-D, JEC, MEM, SaLa, PAT, CA-H, WSB, MCA, DCC, ShSr, JCC, GP, GC, MJR, GJ, RHNS, JJH, MaSa, RV, RM-C, MT, NM, SIB, SKVDE, DFE, SJC, MBC, FW, HN, JSW, RAE, ZK-J, CAH. CAH and RAE had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Author Contributions
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/s41588-020-00748-0