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Record W3115151307 · doi:10.1038/s41588-020-00748-0

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

2021· review· en· W3115151307 on OpenAlexaff
David V. Conti, Burcu F. Darst, Lilit C. Moss, Edward J. Saunders, Xin Sheng, Alisha Chou, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Ali Sahimi, Thomas J. Hoffmann, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Kenneth Muir, Artitaya Lophatananon, Peggy Wan, Loı̈c Le Marchand, Lynne R. Wilkens, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Røder, Peter Iversen, Jyotsna Batra, Suzanne K. Chambers, Leire Moya, Lisa G. Horvath, Judith A. Clements, Wayne D. Tilley, Gail P. Risbridger, Henrik Grönberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordström, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Timothy J. Key, Elio Ríboli, Jong Y. Park, Thomas A. Sellers, Hui‐Yi Lin, Demetrius Albanes, Stephanie J. Weinstein, Lorelei A. Mucci, Edward L. Giovannucci, Sara Lindström, Peter Kraft, David J. Hunter, Kathryn L. Penney, Constance Turman, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Marie‐Elise Parent, Janet L. Stanford, Elaine A. Ostrander, Milan S. Geybels, Stella Koutros, Laura E. Beane Freeman, Meir J. Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Karina D. Sørensen, Michael Borre, William J. Blot, Wei Zheng, Edward D. Yeboah, James E. Mensah, Yong‐Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan‐Chao Zhao, Zan Sun, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Catharine West, N.G. Burnet, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Géraldine Cancel‐Tassin, F. Ménégaux, Thérèse Truong, Yves Akoli Koudou, Esther M. John, Eli Marie Grindedal, Lovise Mæhle, Kay‐Tee Khaw, Sue A. Ingles, Mariana C. Stern, Ana Vega, Antonio Gómez‐Caamaño, Laura Fachal, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Manuel R. Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T. Bensen, Elizabeth T. H. Fontham, James L. Mohler, Jack A. Taylor, Manolis Kogevinas, Javier Llorca, Gemma Castaño‐Vinyals, Lisa Cannon‐Albright, Craig C. Teerlink, Chad D. Huff, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Brandi Weaver, Hermann Brenner, Katarina Ćuk, Bernd Holleczek, Kai-Uwe Saum, Eric A. Klein, Ann W. Hsing, Rick A. Kittles, Adam B. Murphy, Christopher J. Logothetis, Jeri Kim, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, William B. Isaacs, Barbara Nemesure, Anselm Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Hassan Abdul Razack, Jasmine Lim, Soo‐Hwang Teo, Lisa F. Newcomb, Daniel Lin, Jay H. Fowke, Christine Neslund‐Dudas, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kuliš, Nawaid Usmani, Sandeep K. Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Domínguez, Jose E. Castelao, Marı́a Elena Martı́nez, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, William S. Bush, Melinda C. Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer Cullen, György Petrovics, Graham Casey, Monique J. Roobol, Guido Jenster, Ron H. N. van Schaik, Jennifer J. Hu, Maureen Sanderson, Rohit Varma, Roberta McKean‐Cowdin, Mina Torres, Nicholas Mancuso, Sonja I. Berndt, Stephen K. Van Den Eeden, Douglas F. Easton, Stephen J. Chanock, Michael B. Cook, Fredrik Wiklund, Hidewaki Nakagawa, Rosalind A. Eeles, Zsofia Kote‐Jarai, Christopher A. Haiman

Bibliographic record

VenueNature Genetics · 2021
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of AlbertaUniversité de MontréalPrincess Margaret Cancer CentreInstitut National de la Recherche ScientifiqueUniversity of Toronto
FundersMedical Research CouncilEuropean Society for Medical OncologyNational Cancer InstituteNational Institutes of HealthU.S. Department of Health and Human ServicesCancer Research UKWellcome TrustNational Institute of Environmental Health SciencesIpsenNational Institute for Health and Care ResearchAchievement Rewards for College Scientists Foundation
KeywordsProstate cancerOdds ratioBiologyGenome-wide association studyGenetic genealogyPopulationConfidence intervalDemographyGeneticsCancerOncologyInternal medicineSingle-nucleotide polymorphismMedicineGenotypeGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.032
GPT teacher head0.330
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations500
Published2021
Admission routes1
Has abstractyes

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