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Record W3177326348 · doi:10.20517/jtgg.2021.08

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes

2021· article· en· W3177326348 on OpenAlexafffund
Amy Moore, Mitchell J. Machiela, Moara Machado, Sophia Wang, Eleanor Kane, Susan L. Slager, Weiyin Zhou, Mary Carrington, Qing Lan, Roger L. Milne, Brenda M. Birmann, Hans‐Olov Adami, Demetrius Albanes, Alan A. Arslan, Nikolaus Becker, Yolanda Benavente, Simonetta Bisanzi, Paolo Boffetta, Paige M. Bracci, Paul Brennan, Angela Brooks‐Wilson, Federico Canzian, Neil E. Caporaso, Jacqueline Clavel, Pierluigi Cocco, Lucía Conde, David G. Cox, Wendy Cozen, Karen Curtin, Immaculata De Vivo, Sílvia de Sanjosé, Lenka Foretová, Susan M. Gapstur, Hervé Ghesquières, Graham G. Giles, Martha Glenn, Bengt Glimelius, Chi Gao, Thomas M. Habermann, Henrik Hjalgrim, Rebecca D. Jackson, Mark Liebow, Brian K. Link, Marc Maynadié, James McKay, Mads Melbye, Lucia Miligi, Thierry Jo Molina, Alain Monnereau, Alexandra Nieters, Kari E. North, Kenneth Offit, Alpa V. Patel, Sara Piro, Vignesh Ravichandran, Elio Ríboli, Gilles Salles, Richard K. Severson, Christine F. Skibola, Karin E. Smedby, Melissa C. Southey, John J. Spinelli, Anthony Staines, Carolyn Stewart, Lauren R. Teras, Lesley F. Tinker, Ruth C. Travis, Claire M. Vajdic, Roel Vermeulen, Joseph Vijai, Elisabete Weiderpass, Stephanie J. Weinstein, Nicole Wong Doo, Yawei Zhang, Tongzhang Zheng, Stephen J. Chanock, Nathaniel Rothman, James R. Cerhan, Michael Dean, Nicola J. Camp, Meredith Yeager, Sonja I. Berndt

Bibliographic record

VenueJournal of Translational Genetics and Genomics · 2021
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsSimon Fraser University
FundersDivision of Cancer Epidemiology and Genetics, National Cancer InstituteKræftens BekæmpelseNational Human Genome Research InstituteDeutsche KrebshilfeNational Center for Chronic Disease Prevention and Health PromotionNational Heart, Lung, and Blood InstituteNational Institute on AgingBC Cancer AgencyWorld Cancer Research FundNational Center for Advancing Translational SciencesMedical Research CouncilInstitut National Du CancerCenters for Disease Control and PreventionNational Institutes of HealthNational Institute of Environmental Health SciencesHellenic Health FoundationCancer Research UKBlood Cancer UKInstitut Gustave-RoussyAssociazione Italiana per la Ricerca sul CancroAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailNordForskVetenskapsrådetCanadian Institutes of Health ResearchMedStar Health Research InstituteCancerfondenMichael Smith Health Research BCCentres de Recerca de CatalunyaInstitut National de la Santé et de la Recherche MédicaleU.S. Department of Health and Human ServicesFrederick National Laboratory for Cancer ResearchGeneralitat de CatalunyaFondation de FranceDeutsches KrebsforschungszentrumLigue Contre le CancerEuropean Regional Development FundBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadUniversity of PittsburghWorld Health OrganizationNational Cancer InstituteOhio State UniversityInstituto de Salud Carlos IIIWake Forest UniversityAmerican Cancer SocietyBrigham and Women's HospitalUniversity at BuffaloEuropean Commission
KeywordsLymphomaGenomeRuns of HomozygosityGeneticsBiologyHodgkin lymphomaMedicineGenotypeSingle-nucleotide polymorphismGeneImmunology

Abstract

fetched live from OpenAlex

AIM: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. METHODS: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. RESULTS: ). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. CONCLUSION: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

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)0.000
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 score0.208
Threshold uncertainty score0.562

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 integrity0.0000.000
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 head0.016
GPT teacher head0.260
Teacher spread0.244 · 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".

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Citations0
Published2021
Admission routes2
Has abstractyes

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