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Record W3120866514 · doi:10.1038/s41467-020-20368-w

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

2021· article· en· W3120866514 on OpenAlexafffund
Jue‐Sheng Ong, Suzanne C. Dixon‐Suen, Xikun Han, Jiyuan An, Rebecca C. Fitzgerald, Matt Buas, Marilie D. Gammon, Douglas A. Corley, Nicholas J. Shaheen, Laura J. Hardie, Nigel C. Bird, Brian J. Reid, Wong‐Ho Chow, Harvey A. Risch, Weimin Ye, Geoffrey Liu, Yvonne Romero, Leslie Bernstein, Anna H. Wu, David E. Whiteman, Thomas E. Vaughan, Michelle Agee, Babak Alipanahi, A. Auton, R. K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, D. A. Hinds, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, M. H. McIntyre, J. L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, C Tian, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Upekha E. Liyanage, Jean-Cluade Dusingize, Johannes Schumacher, Ines Gockel, Anne C. Böhmer, Janusz Jankowski, Claire Palles, Tracy A. O’Mara, Amanda B. Spurdle, Matthew H. Law, Mark M. Iles, Paul D.P. Pharoah, Andrew Berchuck, Wei Zheng, Aaron P. Thrift, Catherine M. Olsen, Rachel Ε. Neale, Puya Gharahkhani, Penelope M. Webb, Stuart MacGregor

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOntario Institute for Cancer Research
FundersCancer Council VictoriaMedical Research CouncilCanadian Institutes of Health ResearchNorthwest Regional Development AgencyDiabetes UKNational Cancer InstituteBritish Heart FoundationNational Institute for Health and Care ResearchQIMR Berghofer Medical Research InstituteProstate Cancer Foundation of AustraliaCancer Research InstituteRoyal Marsden NHS Foundation TrustRosetrees TrustEuropean CommissionPancreatic Cancer UKBreast Cancer Research FoundationWellcome TrustProstate Cancer FoundationNational Cancer Research InstituteNational Institutes of HealthOvarian Cancer Research FundNational Health and Medical Research CouncilCancer Research UK
KeywordsMendelian randomizationPleiotropySingle-nucleotide polymorphismCancerVitamin D and neurologyOvarian cancerConfidence intervalInternal medicineMedicineOncologyBioinformaticsBiologyGeneticsGenetic variantsGenePhenotypeGenotype

Abstract

fetched live from OpenAlex

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

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)0.034
metaresearch head score (Gemma)0.078
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: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.034
Threshold uncertainty score0.181

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0340.078
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0030.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0050.001

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 head0.031
GPT teacher head0.359
Teacher spread0.329 · 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".

Quick stats

Citations59
Published2021
Admission routes2
Has abstractyes

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