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Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach

2021· preprint· en· W3186350383 on OpenAlexaff
Serena A. Dodhia, Nicola West, Steven J. Thomas, Nicholas J. Timpson, Ingegerd Johansson, Pernilla Lif Holgerson, Tom Dudding, Simon Haworth

Bibliographic record

VenueWellcome Open Research · 2021
Typepreprint
Languageen
FieldMedicine
TopicVitamin D Research Studies
Canadian institutionsUniversity of Manitoba
FundersMedical Research CouncilUniversity of BristolWellcome TrustAcademy of Medical SciencesNational Institute for Health and Care ResearchNIHR Bristol Biomedical Research CentreCancer Research UK
KeywordsMendelian randomizationConfoundingCausal inferenceMedicineVitamin D and neurologyMarginal structural modelOdds ratioInternal medicineDemographyBiologyGeneticsGenotypePathology

Abstract

fetched live from OpenAlex

Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome. Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years). Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68) Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.

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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)0.063
metaresearch head score (Gemma)0.142
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.063
Threshold uncertainty score0.333

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0630.142
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.003
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0060.001

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 head0.098
GPT teacher head0.378
Teacher spread0.280 · 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 designSimulation or modeling
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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Citations5
Published2021
Admission routes1
Has abstractyes

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