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


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.

SUBMITTER: Conti DV 

PROVIDER: S-EPMC8148035 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Conti David V DV   Darst Burcu F BF   Moss Lilit C LC   Saunders Edward J EJ   Sheng Xin X   Chou Alisha A   Schumacher Fredrick R FR   Olama Ali Amin Al AAA   Benlloch Sara S   Dadaev Tokhir T   Brook Mark N MN   Sahimi Ali A   Hoffmann Thomas J TJ   Takahashi Atushi A   Matsuda Koichi K   Momozawa Yukihide Y   Fujita Masashi M   Muir Kenneth K   Lophatananon Artitaya A   Wan Peggy P   Le Marchand Loic L   Wilkens Lynne R LR   Stevens Victoria L VL   Gapstur Susan M SM   Carter Brian D BD   Schleutker Johanna J   Tammela Teuvo L J TLJ   Sipeky Csilla C   Auvinen Anssi A   Giles Graham G GG   Southey Melissa C MC   MacInnis Robert J RJ   Cybulski Cezary C   Wokołorczyk Dominika D   Lubiński Jan J   Neal David E DE   Donovan Jenny L JL   Hamdy Freddie C FC   Martin Richard M RM   Nordestgaard Børge G BG   Nielsen Sune F SF   Weischer Maren M   Bojesen Stig E SE   Røder Martin Andreas MA   Iversen Peter P   Batra Jyotsna J   Chambers Suzanne S   Moya Leire L   Horvath Lisa L   Clements Judith A JA   Tilley Wayne W   Risbridger Gail P GP   Gronberg Henrik H   Aly Markus M   Szulkin Robert R   Eklund Martin M   Nordström Tobias T   Pashayan Nora N   Dunning Alison M AM   Ghoussaini Maya M   Travis Ruth C RC   Key Tim J TJ   Riboli Elio E   Park Jong Y JY   Sellers Thomas A TA   Lin Hui-Yi HY   Albanes Demetrius D   Weinstein Stephanie J SJ   Mucci Lorelei A LA   Giovannucci Edward E   Lindstrom Sara S   Kraft Peter P   Hunter David J DJ   Penney Kathryn L KL   Turman Constance C   Tangen Catherine M CM   Goodman Phyllis J PJ   Thompson Ian M IM   Hamilton Robert J RJ   Fleshner Neil E NE   Finelli Antonio A   Parent Marie-Élise MÉ   Stanford Janet L JL   Ostrander Elaine A EA   Geybels Milan S MS   Koutros Stella S   Freeman Laura E Beane LEB   Stampfer Meir M   Wolk Alicja A   Håkansson Niclas N   Andriole Gerald L GL   Hoover Robert N RN   Machiela Mitchell J MJ   Sørensen Karina Dalsgaard KD   Borre Michael M   Blot William J WJ   Zheng Wei W   Yeboah Edward D ED   Mensah James E JE   Lu Yong-Jie YJ   Zhang Hong-Wei HW   Feng Ninghan N   Mao Xueying X   Wu Yudong Y   Zhao Shan-Chao SC   Sun Zan Z   Thibodeau Stephen N SN   McDonnell Shannon K SK   Schaid Daniel J DJ   West Catharine M L CML   Burnet Neil N   Barnett Gill G   Maier Christiane C   Schnoeller Thomas T   Luedeke Manuel M   Kibel Adam S AS   Drake Bettina F BF   Cussenot Olivier O   Cancel-Tassin Géraldine G   Menegaux Florence F   Truong Thérèse T   Koudou Yves Akoli YA   John Esther M EM   Grindedal Eli Marie EM   Maehle Lovise L   Khaw Kay-Tee KT   Ingles Sue A SA   Stern Mariana C MC   Vega Ana A   Gómez-Caamaño Antonio A   Fachal Laura L   Rosenstein Barry S BS   Kerns Sarah L SL   Ostrer Harry H   Teixeira Manuel R MR   Paulo Paula P   Brandão Andreia A   Watya Stephen S   Lubwama Alexander A   Bensen Jeannette T JT   Fontham Elizabeth T H ETH   Mohler James J   Taylor Jack A JA   Kogevinas Manolis M   Llorca Javier J   Castaño-Vinyals Gemma G   Cannon-Albright Lisa L   Teerlink Craig C CC   Huff Chad D CD   Strom Sara S SS   Multigner Luc L   Blanchet Pascal P   Brureau Laurent L   Kaneva Radka R   Slavov Chavdar C   Mitev Vanio V   Leach Robin J RJ   Weaver Brandi B   Brenner Hermann H   Cuk Katarina K   Holleczek Bernd B   Saum Kai-Uwe KU   Klein Eric A EA   Hsing Ann W AW   Kittles Rick A RA   Murphy Adam B AB   Logothetis Christopher J CJ   Kim Jeri J   Neuhausen Susan L SL   Steele Linda L   Ding Yuan Chun YC   Isaacs William B WB   Nemesure Barbara B   Hennis Anselm J M AJM   Carpten John J   Pandha Hardev H   Michael Agnieszka A   De Ruyck Kim K   De Meerleer Gert G   Ost Piet P   Xu Jianfeng J   Razack Azad A   Lim Jasmine J   Teo Soo-Hwang SH   Newcomb Lisa F LF   Lin Daniel W DW   Fowke Jay H JH   Neslund-Dudas Christine C   Rybicki Benjamin A BA   Gamulin Marija M   Lessel Davor D   Kulis Tomislav T   Usmani Nawaid N   Singhal Sandeep S   Parliament Matthew M   Claessens Frank F   Joniau Steven S   Van den Broeck Thomas T   Gago-Dominguez Manuela M   Castelao Jose Esteban JE   Martinez Maria Elena ME   Larkin Samantha S   Townsend Paul A PA   Aukim-Hastie Claire C   Bush William S WS   Aldrich Melinda C MC   Crawford Dana C DC   Srivastava Shiv S   Cullen Jennifer C JC   Petrovics Gyorgy G   Casey Graham G   Roobol Monique J MJ   Jenster Guido G   van Schaik Ron H N RHN   Hu Jennifer J JJ   Sanderson Maureen M   Varma Rohit R   McKean-Cowdin Roberta R   Torres Mina M   Mancuso Nicholas N   Berndt Sonja I SI   Van Den Eeden Stephen K SK   Easton Douglas F DF   Chanock Stephen J SJ   Cook Michael B MB   Wiklund Fredrik F   Nakagawa Hidewaki H   Witte John S JS   Eeles Rosalind A RA   Kote-Jarai Zsofia Z   Haiman Christopher A CA  

Nature genetics 20210104 1


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  ...[more]

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