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Record W2587523829 · doi:10.1038/ncomms14175

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

2017· article· en· W2587523829 on OpenAlexafffund
Philip Law, Sonja I. Berndt, Helen E. Speedy, Nicola J. Camp, Georgina P. Sava, C.F. Skibola, Amy Holroyd, Joseph Vijai, Nicola J. Sunter, Alexandra Nieters, Sı́lvia Beà, Alain Monnereau, David Martin‐García, Lynn R. Goldin, Guillem Clot, Lauren R. Teras, Inés Quintela, Brenda M. Birmann, Sandrine Jayne, Wendy Cozen, Aneela Majid, Karin E. Smedby, Qing Lan, Claire Dearden, Angela Brooks‐Wilson, Mark P. Purdue, Tryfonia Mainou‐Fowler, Claire M. Vajdic, Graham Jackson, Pierluigi Cocco, Helen Marr, Yawei Zhang, Tongzhang Zheng, Graham G. Giles, Charles Lawrence, Timothy G. Call, Mark Liebow, Mads Melbye, Bengt Glimelius, Larry Mansouri, Martha Glenn, Karen Curtin, W. Ryan Diver, Brian K. Link, Lucía Conde, Paige M. Bracci, Elizabeth A. Holly, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Marc Maynadie, James McKay, Demetrius Albanes, Stephanie J. Weinstein, Zhaoming Wang, Neil E. Caporaso, Lindsay M. Morton, Richard K. Severson, Elio Ríboli, Paolo Vineis, Roel Vermeulen, Melissa C. Southey, Roger L. Milne, Jacqueline Clavel, Sabine Topka, John J. Spinelli, Peter Kraft, Maria Grazia Ennas, Geoffrey Summerfield, Giovanni Maria Ferri, Robert J. Harris, Lucia Miligi, Andrew R. Pettitt, Kari E. North, David Allsup, Joseph F. Fraumeni, James R Bailey, Kenneth Offit, Guy Pratt, Henrik Hjalgrim, Chris Pepper, Stephen J. Chanock, Chris Fegan, Richard Rosenquist, Sílvia de Sanjosé, Ángel Carracedo, Martin J.S. Dyer, Daniel Catovsky, Elı́as Campo, James R. Cerhan, James M. Allan, Nathanial Rothman, Richard S. Houlston, Susan L. Slager

Bibliographic record

VenueNature Communications · 2017
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of British ColumbiaSimon Fraser UniversityBC Cancer Agency
FundersNational Center for Advancing Translational SciencesNational Center for Chronic Disease Prevention and Health PromotionNational Institute of Environmental Health SciencesNational Cancer InstituteNational Heart, Lung, and Blood InstituteNational Institute on AgingCancer Council NSWNational Human Genome Research InstituteCancer Council VictoriaMedical Research CouncilUniversity of Texas MD Anderson Cancer CenterInstitut National Du CancerCenters for Disease Control and PreventionNational Institutes of HealthAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailU.S. Public Health ServiceUniversity at BuffaloRegione Autonoma della SardegnaAssociazione Italiana per la Ricerca sul CancroUniversity of UtahFondation de FranceGeneralitat de CatalunyaCanadian Institutes of Health ResearchBundesamt für StrahlenschutzMedStar Health Research InstituteCancerfondenMinisterio de Economía y CompetitividadBundesministerium für Bildung und ForschungUniversity of SydneyDivision of Cancer Prevention, National Cancer InstituteHealth Research BoardNational Health and Medical Research CouncilLeukemia and Lymphoma ResearchStockholms Läns LandstingUniversity of PittsburghDivision of Cancer Epidemiology and Genetics, National Cancer InstituteHuntsman Cancer InstituteJosé Carreras Leukämie-StiftungWellcome TrustMemorial Sloan-Kettering Cancer CenterYale UniversityKarolinska InstitutetUtah State UniversityEuropean CommissionU.S. Department of Veterans AffairsCompagnia di San PaoloLeukemia and Lymphoma SocietyUtah Department of HealthBrigham and Women's HospitalUniversity of California, San FranciscoU.S. Department of Health and Human ServicesInstituto de Salud Carlos IIIWake Forest UniversityOhio State UniversityCancer Research UKWorld Health OrganizationUniversity of Southern CaliforniaAmerican Cancer SocietyMichael Smith Health Research BC
KeywordsGeneGeneticsBiologyImmune dysregulationGenomeTranscription factorGenome-wide association studyImmune systemChromatinSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223,P=5.04 × 10−13), 1q42.13 (rs41271473,P=1.06 × 10−10), 4q24 (rs71597109,P=1.37 × 10−10), 4q35.1 (rs57214277,P=3.69 × 10−8), 6p21.31 (rs3800461,P=1.97 × 10−8), 11q23.2 (rs61904987,P=2.64 × 10−11), 18q21.1 (rs1036935,P=3.27 × 10−8), 19p13.3 (rs7254272,P=4.67 × 10−8) and 22q13.33 (rs140522,P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

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)0.003
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.004
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.029
GPT teacher head0.360
Teacher spread0.331 · 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 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".

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Citations104
Published2017
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicChronic Lymphocytic Leukemia ResearchFrench-language works237,207