MétaCan
Menu
Back to cohort
Record W4388541037 · doi:10.1038/s41588-023-01534-4

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

2023· article· en· W4388541037 on OpenAlexafffund
Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha Chou, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Anna Plym, Ali Sahimi, Thomas J. Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Yamanashi, Yoshinori Murakami, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Masahiko Higashiyama, Akihide Masumoto, Yuji Uchio, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy Pal Choudhury, Johanna Schleutker, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, Christopher T. Rentsch, Kelly Cho, Benjamin H. McMahon, 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, Hein Vincent Stroomberg, Jyotsna Batra, Suzanne K. Chambers, 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, Michael B. Cook, 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‐Élise Parent, Janet L. Stanford, Elaine A. Ostrander, 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, James E. Mensah, Yong‐Jie Lu, Hongwei Zhang, Ninghan Feng, Xueying Mao, Shan‐Chao Zhao, Zan Sun, Shannon K. McDonnell, Daniel J. Schaid, Catharine West, 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, Jeannette T. Bensen, Eboneé N. Butler, James L. Mohler, Jack A. Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño‐Vinyals, Lisa Cannon‐Albright, Chad Huff, Patrick G. Pilié, Yao Yu, Ryan J. Bohlender, Jian Gu, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, 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 J. M. Hennis, John D. Carpten, Hardev Pandha, Agnieszka Michael, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Hassan Abdul Razack, Jasmine Lim, Soo‐Hwang Teo, Lisa F. Newcomb, Daniel Lin, Jay H. Fowke, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kuliš, Sandeep K. Singhal, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Domínguez, Jose E. Castelao, Maria Elena Martinez, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, William S. Bush, Melinda C. Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer Cullen, György Petrovics, Ying Wang, Joseph Lachance, Wei Tang, Richard Biritwum, Andrew A. Adjei, Evelyn Tay, Shelley Niwa, Kosj Yamoah, Anand P. Chokkalingam, Jacob M. Keaton, Jacklyn N. Hellwege, Peter E. Clark, Mohamed Jalloh, Sérigne Maguèye Gueye, Lamine Niang, Olufemi J. Ogunbiyi, Olukemi K. Amodu, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua O.D. Abrahams, Halimatou Diop‐Ndiaye, Susan Gundell, Monique J. Roobol, Guido Jenster, Ron HN van Schaik, Jennifer J. Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta McKean‐Cowdin, Mina Torres, Michael Preuß, Ruth J. F. Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K. Van Den Eeden, Douglas F. Easton, Stefan Ambs, Todd L. Edwards, Reedik Mägi, Timothy R. Rebbeck, Lars G. Fritsche, Stephen J. Chanock, Sonja I. Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S. Witte, J. Michael Gaziano, Amy C. Justice, Nicholas Mancuso, Chikashi Terao, Rosalind A. Eeles, Zsofia Kote‐Jarai, Ravi Madduri, David V. Conti, Christopher A. Haiman

Bibliographic record

VenueNature Genetics · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of AlbertaUniversity of TorontoPrincess Margaret Cancer Centre
FundersCommon FundDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDOD Prostate Cancer Research ProgramHellenic Health FoundationNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Cancer InstituteEllison Medical FoundationInstituto de Salud Carlos IIIWorld Cancer Research FundProstate Cancer FoundationMedical Research CouncilEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentU.S. Department of Health and Human ServicesUniversity of California, San FranciscoNational Institute for Health and Care ResearchVlaamse regeringNovo Nordisk FondenFondation de FranceNational Health and Medical Research CouncilUniversiti MalayaProstate Cancer Foundation of AustraliaVetenskapsrådetNational Institute of Mental HealthKU LeuvenCanadian Institutes of Health ResearchFonds Wetenschappelijk OnderzoekCancerfondenBreast Cancer Research FoundationUniversity of CambridgeU.S. Department of DefenseCancer Research UKAustralian GovernmentOvarian Cancer Research FundBundesministerium für Bildung und ForschungSwedish Cancer FoundationDeutsches KrebsforschungszentrumAssociazione Italiana per la Ricerca sul CancroNational Center for Advancing Translational SciencesKaiser PermanenteFondation ARC pour la Recherche sur le CancerNational Cancer Research InstituteRoyal Marsden NHS Foundation TrustEuropean CommissionCancer Council VictoriaDeutsche KrebshilfeOffice of Research and DevelopmentNational Institute on AgingWayne and Gladys Valley FoundationInstitut National Du CancerCancer Research InstituteNational Institutes of HealthRobert Wood Johnson Foundation
KeywordsProstate cancerBiologyGenome-wide association studyDiseaseGenetic genealogyGeneticsGenetic association1000 Genomes ProjectCancerAncestry-informative markerProstateSingle-nucleotide polymorphismOncologyGenotypeInternal medicineGeneMedicinePopulationEnvironmental health

Abstract

fetched live from OpenAlex

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups. A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.194
Threshold uncertainty score0.986

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.020
GPT teacher head0.301
Teacher spread0.281 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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

Citations143
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueNature GeneticsSame topicGenetic Associations and EpidemiologyFrench-language works237,207