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Record W4406536713 · doi:10.1002/gepi.22612

A Novel Statistical Method for Unmasking Sex‐Specific Genomics Signatures in Complex Traits

2025· article· en· W4406536713 on OpenAlexafffund
Samaneh Mansouri, Benoît Labonté, Qingrun Zhang, Ting‐Huei Chen

Bibliographic record

VenueGenetic Epidemiology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsAlberta Children's HospitalUniversity of CalgaryUniversité Laval
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsComputational biologyBiologyGenomicsEvolutionary biologyGeneticsGenomeGene

Abstract

fetched live from OpenAlex

Genotype-phenotype association studies have advanced our understanding of complex traits but often overlook sex-specific genetic signals. The growing awareness of sex-specific influences on human traits and diseases necessitates tailored statistical methodologies to dissect these genetic intricacies. Rare genetic variants play a significant role in disease development, often exhibiting stronger per-allele effects than common variants. In sex-dimorphic analysis, traits are viewed as having two sex-specific subsets rather than being uniformly defined. Existing methods for gene-based analysis of rare variants across multiple traits can identify shared genetic signals but cannot reveal the specific subsets from which significant signals originate. This means that when a significant signal is detected, it remains unclear whether it arises from the male samples, female samples, or both. To address this limitation, we propose SubsetRV, a new methodology capable of identifying genes associated with specific traits or diseases in males, females, or both. SubsetRV can also be applied to broader applications in multiple traits analysis. Simulation studies have demonstrated SubsetRV's reliability, and real data analysis on bipolar disorder and schizophrenia has revealed potential sex-specific genetic signals. SubsetRV offers a valuable tool for identifying sex-specific genetic candidates, aiding in understanding disease mechanisms. An R package for SubsetRV is available on GitHub. It can be accessed directly through this link: https://github.com/Mansouri-S/SubsetRV.

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)0.002
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.489
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
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 head0.053
GPT teacher head0.366
Teacher spread0.314 · 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.

Study designObservational
Domainnot available
GenreMethods

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

Citations0
Published2025
Admission routes2
Has abstractyes

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