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

Conti, DV; Darst, BF; Moss, LC; Saunders, EJ; Sheng, X; Chou, A; Schumacher, FR; Al Olama, AA; Benlloch, S; Dadaev, T; Brook, MN; Sahimi, A; Hoffmann, TJ; Takahashi, A; Matsuda, K; Momozawa, Y; Fujita, M; Muir, K; Lophatananon, A; Wan, P; Le Marchand, L; Wilkens, LR; Stevens, VL; Gapstur, SM; Carter, BD; Schleutker, J; Tammela, TLJ; Sipeky, C; Auvinen, A; Giles, GG; Southey, MC; MacInnis, RJ; Cybulski, C; Wokolorczyk, D; Lubinski, J; Neal, DE; Donovan, JL; Hamdy, FC; Martin, RM; Nordestgaard, BG; Nielsen, SF; Weischer, M; Bojesen, SE; Roder, MA; Iversen, P; Batra, J; Chambers, S; Moya, L; Horvath, L; Clements, JA; Tilley, W; Risbridger, GP; Gronberg, H; Aly, M; Szulkin, R; Eklund, M; Nordstrom, T; Pashayan, N; Dunning, AM; Ghoussaini, M; Travis, RC; Key, TJ; Riboli, E; Park, JY; Sellers, TA; Lin, HY; Albanes, D; Weinstein, SJ; Mucci, LA; Giovannucci, E; Lindstrom, S; Kraft, P; Hunter, DJ; Penney, KL; Turman, C; Tangen, CM; Goodman, PJ; Thompson, IM, Jr; Hamilton, RJ; Fleshner, NE; Finelli, A; Parent, ME; Stanford, JL; Ostrander, EA; Geybels, MS; Koutros, S; Freeman, LEB; Stampfer, M; Wolk, A; Hakansson, N; Andriole, GL; Hoover, RN; Machiela, MJ; Sorensen, KD; Borre, M; Blot, WJ; Zheng, W; Yeboah, ED; Mensah, JE; Lu, YJ; Zhang, HW; Feng, N; Mao, X; Wu, Y; Zhao, SC; Sun, Z; Thibodeau, SN; McDonnell, SK; Schaid, DJ; West, CML; Burnet, N; Barnett, G; Maier, C; Schnoeller, T; Luedeke, M; Kibel, AS; Drake, BF; Cussenot, O; Cancel-Tassin, G; Menegaux, F; Truong, T; Koudou, YA; John, EM; Grindedal, EM; Maehle, L; Khaw, KT; Ingles, SA; Stern, MC; Vega, A; Gomez-Caamano, A; Fachal, L; Rosenstein, BS; Kerns, SL; Ostrer, H; Teixeira, MR; Paulo, P; Brandao, A; Watya, S; Lubwama, A; Bensen, JT; Fontham, ETH; Mohler, J; Taylor, JA; Kogevinas, M; Llorca, J; Castano-Vinyals, G; Cannon-Albright, L; Teerlink, CC; Huff, CD; Strom, SS; Multigner, L; Blanchet, P; Brureau, L; Kaneva, R; Slavov, C; Mitev, V; Leach, RJ; Weaver, B; Brenner, H; Cuk, K; Holleczek, B; Saum, KU; Klein, EA; Hsing, AW; Kittles, RA; Murphy, AB; Logothetis, CJ; Kim, J; Neuhausen, SL; Steele, L; Ding, YC; Isaacs, WB; Nemesure, B; Hennis, AJM; Carpten, J; Pandha, H; Michael, A; De Ruyck, K; De Meerleer, G; Ost, P; Xu, J; Razack, A; Lim, J; Teo, SH; Newcomb, LF; Lin, DW; Fowke, JH; Neslund-Dudas, C; Rybicki, BA; Gamulin, M; Lessel, D; Kulis, T; Usmani, N; Singhal, S; Parliament, M; Claessens, F; Joniau, S; Van den Broeck, T; Gago-Dominguez, M; Castelao, JE; Martinez, ME; Larkin, S; Townsend, PA; Aukim-Hastie, C; Bush, WS; Aldrich, MC; Crawford, DC; Srivastava, S; Cullen, JC; Petrovics, G; Casey, G; Roobol, MJ; Jenster, G; van Schaik, RHN; Hu, JJ; Sanderson, M; Varma, R; McKean-Cowdin, R; Torres, M; Mancuso, N; Berndt, SI; Van Den Eeden, SK; Easton, DF; Chanock, SJ; Cook, MB; Wiklund, F; Nakagawa, H; Witte, JS; Eeles, RA; Kote-Jarai, Z; Haiman, CA

Author(s): Conti, DV; Darst, BF; Moss, LC; Saunders, EJ; Sheng, X; Chou, A; Schumacher, FR; Al Olama, AA; Benlloch, S; Dadaev, T; Brook, MN; Sahimi, A; Hoffmann, TJ; Takahashi, A; Matsuda, K; Momozawa, Y; Fujita, M; Muir, K; Lophatananon, A; Wan, P; Le Marchand, L; Wilkens, LR; Stevens, VL; Gapstur, SM; Carter, BD; Schleutker, J; Tammela, TLJ; Sipeky, C; Auvinen, A; Giles, GG; Southey, MC; MacInnis, RJ; Cybulski, C; Wokolorczyk, D; Lubinski, J; Neal, DE; Donovan, JL; Hamdy, FC; Martin, RM; Nordestgaard, BG; Nielsen, SF; Weischer, M; Bojesen, SE; Roder, MA; Iversen, P; Batra, J; Chambers, S; Moya, L; Horvath, L; Clements, JA; Tilley, W; Risbridger, GP; Gronberg, H; Aly, M; Szulkin, R; Eklund, M; Nordstrom, T; Pashayan, N; Dunning, AM; Ghoussaini, M; Travis, RC; Key, TJ; Riboli, E; Park, JY; Sellers, TA; Lin, HY; Albanes, D; Weinstein, SJ; Mucci, LA; Giovannucci, E; Lindstrom, S; Kraft, P; Hunter, DJ; Penney, KL; Turman, C; Tangen, CM; Goodman, PJ; Thompson, IM, Jr; Hamilton, RJ; Fleshner, NE; Finelli, A; Parent, ME; Stanford, JL; Ostrander, EA; Geybels, MS; Koutros, S; Freeman, LEB; Stampfer, M; Wolk, A; Hakansson, N; Andriole, GL; Hoover, RN; Machiela, MJ; Sorensen, KD; Borre, M; Blot, WJ; Zheng, W; Yeboah, ED; Mensah, JE; Lu, YJ; Zhang, HW; Feng, N; Mao, X; Wu, Y; Zhao, SC; Sun, Z; Thibodeau, SN; McDonnell, SK; Schaid, DJ; West, CML; Burnet, N; Barnett, G; Maier, C; Schnoeller, T; Luedeke, M; Kibel, AS; Drake, BF; Cussenot, O; Cancel-Tassin, G; Menegaux, F; Truong, T; Koudou, YA; John, EM; Grindedal, EM; Maehle, L; Khaw, KT; Ingles, SA; Stern, MC; Vega, A; Gomez-Caamano, A; Fachal, L; Rosenstein, BS; Kerns, SL; Ostrer, H; Teixeira, MR; Paulo, P; Brandao, A; Watya, S; Lubwama, A; Bensen, JT; Fontham, ETH; Mohler, J; Taylor, JA; Kogevinas, M; Llorca, J; Castano-Vinyals, G; Cannon-Albright, L; Teerlink, CC; Huff, CD; Strom, SS; Multigner, L; Blanchet, P; Brureau, L; Kaneva, R; Slavov, C; Mitev, V; Leach, RJ; Weaver, B; Brenner, H; Cuk, K; Holleczek, B; Saum, KU; Klein, EA; Hsing, AW; Kittles, RA; Murphy, AB; Logothetis, CJ; Kim, J; Neuhausen, SL; Steele, L; Ding, YC; Isaacs, WB; Nemesure, B; Hennis, AJM; Carpten, J; Pandha, H; Michael, A; De Ruyck, K; De Meerleer, G; Ost, P; Xu, J; Razack, A; Lim, J; Teo, SH; Newcomb, LF; Lin, DW; Fowke, JH; Neslund-Dudas, C; Rybicki, BA; Gamulin, M; Lessel, D; Kulis, T; Usmani, N; Singhal, S; Parliament, M; Claessens, F; Joniau, S; Van den Broeck, T; Gago-Dominguez, M; Castelao, JE; Martinez, ME; Larkin, S; Townsend, PA; Aukim-Hastie, C; Bush, WS; Aldrich, MC; Crawford, DC; Srivastava, S; Cullen, JC; Petrovics, G; Casey, G; Roobol, MJ; Jenster, G; van Schaik, RHN; Hu, JJ; Sanderson, M; Varma, R; McKean-Cowdin, R; Torres, M; Mancuso, N; Berndt, SI; Van Den Eeden, SK; Easton, DF; Chanock, SJ; Cook, MB; Wiklund, F; Nakagawa, H; Witte, JS; Eeles, RA; Kote-Jarai, Z; Haiman, CA;
Details: Publication Year 2021-01,Volume 53,Issue #1,Page 65-75
Journal Title: Nature Genetics
Publication Type: Research article
Abstract: 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.
Keywords: *Genetic Loci; *Genetic Predisposition to Disease; *Genome-Wide Association Study; Humans; Male; Middle Aged; Molecular Sequence Annotation; Neoplasm Invasiveness; Odds Ratio; Prostatic Neoplasms/diagnosis/*genetics; Racial Groups/*genetics; Risk Factors
Department(s): Laboratory Research
PubMed ID: 33398198
Publisher's Version: https://doi.org/10.1038/s41588-020-00748-0
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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