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Record W2944046200 · doi:10.1038/s41467-019-09775-w

Association analyses identify 31 new risk loci for colorectal cancer susceptibility

2019· article· en· W2944046200 on OpenAlexaff
Philip Law, Maria Timofeeva, Ceres Fernández–Rozadilla, Peter Broderick, James B. Studd, Juan Fernández‐Tajes, Susan M. Farrington, Victoria Svinti, Claire Palles, Giulia Orlando, Amit Sud, Amy Holroyd, Steven Penegar, Evropi Τheodoratou, P G Vaughan-Shaw, Harry Campbell, Lina Zgaga, Caroline Hayward, Archie Campbell, Sarah E. Harris, Ian J. Deary, John M. Starr, Laura Gatcombe, Sarah Briggs, Lynn Martin, Emma Jaeger, Archana Sharma‐Oates, James E. East, Simon J. Leedham, Roland Arnold, Elaine Johnstone, Haitao Wang, David Kerr, Rachel Kerr, Tim Maughan, Richard Kaplan, Nada Al Tassan, Kimmo Palin, Ulrika A. Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti‐Pekka Sarin, Johan G. Eriksson, Harri Rissanen, Paul Knekt, ­Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Laura Renkonen‐Sinisalo, Anna Lepistö, J. Böhm, Jukka‐Pekka Mecklin, Daniel D. Buchanan, Aung Ko Win, John L. Hopper, Mark A. Jenkins, Noralane M. Lindor, Polly A. Newcomb, Steven Gallinger, David Duggan, Graham Casey, Per Hoffmann, Markus M. Nöthen, Karl‐Heinz Jöckel, Douglas F. Easton, Paul D.P. Pharoah, Julian Peto, Federico Canzian, Anthony J. Swerdlow, Rosalind A. Eeles, Zsofia Kote‐Jarai, Kenneth Muir, Nora Pashayan, Brian E. Henderson, Christopher A. Haiman, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen J. Chanock, Susan M. Gapstur, Victoria L. Stevens, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Henrik Grönberg, Johanna Schleutker, Demetrius Albanes, Alicja Wolk, Catharine West, Lorelei A. Mucci, Géraldine Cancel‐Tassin, Stella Koutros, Karina D. Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny Donovan, Ruth C. Travis, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Christiane Maier, Jeri Kim, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Hassan Abdul Razack, Lisa F. Newcomb, Marija Gamulin, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Domínguez, Monique J. Roobol, F. Ménégaux, Kay‐Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, Stephen N. Thibodeau, Andrea Harkin, Karen Allan, John McQueen, James Paul, Timothy Iveson, Mark Saunders, Katja Butterbach, Jenny Chang‐Claude, Michael Hoffmeister, Hermann Brenner, Iva Kirac, Petar Matošević, Philipp Hofer, Stefanie Brezina, Andrea Gsur, Jeremy P. Cheadle, Lauri A. Aaltonen, Ian Tomlinson, Richard S. Houlston, Malcolm G. Dunlop

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldMedicine
TopicGenetic factors in colorectal cancer
Canadian institutionsPrincess Margaret Cancer CentreAlberta Cancer FoundationUniversity of AlbertaLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersFP7 HealthNational Cancer InstituteInstituto de Salud Carlos IIIMedical Research CouncilNational Institutes of HealthUniversity of EdinburghHellenic Health FoundationXunta de GaliciaDirectorate for Biological SciencesHerzfelder'sche FamilienstiftungInstitut Gustave-RoussyMedizinische Universität GrazMutuelle Générale de l'Education NationaleDeutsche KrebshilfeNordForskScottish Funding CouncilTenovusWorld Cancer Research FundAge UKStavros Niarchos FoundationKuopion Yliopistollinen SairaalaSydäntutkimussäätiöOpetus- ja KulttuuriministeriöJane ja Aatos Erkon SäätiöInstitut National de la Santé et de la Recherche MédicaleKarl-Franzens-Universität GrazDeutsche ForschungsgemeinschaftEuropean CommissionAssociazione Italiana per la Ricerca sul CancroNetherlands eScience CenterChief Scientist Office, Scottish Government Health and Social Care DirectorateBundesministerium für Bildung und ForschungChina Scholarship CouncilFoundation for Cardiovascular ResearchAcademy of FinlandNational Institute on Alcohol Abuse and AlcoholismCentre for Cognitive Ageing and Cognitive EpidemiologyNational Institute for Health and Care ResearchCancer Research InstituteNational Cancer Research InstituteRoyal Marsden NHS Foundation TrustScottish GovernmentNational Heart, Lung, and Blood InstituteBiotechnology and Biological Sciences Research CouncilCancer Research UKWellcome TrustCancer Research WalesUniversity of CambridgeCentre International de Recherche sur le CancerLigue Contre le CancerDeutsches KrebsforschungszentrumNational Institute for Social Care and Health Research
KeywordsColorectal cancerGenome-wide association studyGeneticsBiologyMedicineCancerComputational biologySingle-nucleotide polymorphismGenotypeGene

Abstract

fetched live from OpenAlex

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

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)0.002
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 score0.019
Threshold uncertainty score0.592

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.002
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 science0.0010.000
Research integrity0.0000.001
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 head0.049
GPT teacher head0.417
Teacher spread0.368 · 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

Citations272
Published2019
Admission routes1
Has abstractyes

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