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Record W4379051933 · doi:10.1016/j.ajhg.2023.04.009

eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?

2023· review· en· W4379051933 on OpenAlexafffund
Lei Sun, Zhong Wang, Tianyuan Lu, Teri A. Manolio, Andrew D. Paterson

Bibliographic record

VenueThe American Journal of Human Genetics · 2023
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsHospital for Sick ChildrenJewish General HospitalPublic Health OntarioUniversity of Toronto
FundersCanadian Institutes of Health ResearchDefence Science Institute
KeywordsGenome-wide association studyChromosomeGeneticsBiologyX chromosomeGenomeEvolutionary biologySingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

10 years ago, a detailed analysis showed that only 33% of genome-wide association study (GWAS) results included the X chromosome. Multiple recommendations were made to combat such exclusion. Here, we re-surveyed the research landscape to determine whether these earlier recommendations had been translated. Unfortunately, among the genome-wide summary statistics reported in 2021 in the NHGRI-EBI GWAS Catalog, only 25% provided results for the X chromosome and 3% for the Y chromosome, suggesting that the exclusion phenomenon not only persists but has also expanded into an exclusionary problem. Normalizing by physical length of the chromosome, the average number of studies published through November 2022 with genome-wide-significant findings on the X chromosome is ∼1 study/Mb. By contrast, it ranges from ∼6 to ∼16 studies/Mb for chromosomes 4 and 19, respectively. Compared with the autosomal growth rate of ∼0.086 studies/Mb/year over the last decade, studies of the X chromosome grew at less than one-seventh that rate, only ∼0.012 studies/Mb/year. Among the studies that reported significant associations on the X chromosome, we noted extreme heterogeneities in data analysis and reporting of results, suggesting the need for clear guidelines. Unsurprisingly, among the 430 scores sampled from the PolyGenic Score Catalog, 0% contained weights for sex chromosomal SNPs. To overcome the dearth of sex chromosome analyses, we provide five sets of recommendations and future directions. Finally, until the sex chromosomes are included in a whole-genome study, instead of GWASs, we propose such studies would more properly be referred to as "AWASs," meaning "autosome-wide scans."

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)0.167
metaresearch head score (Gemma)0.373
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: Methods · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.833
Threshold uncertainty score0.882

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.1670.373
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.004
Bibliometrics0.0040.005
Science and technology studies0.0030.010
Scholarly communication0.0090.017
Open science0.0040.005
Research integrity0.0070.020
Insufficient payload (model declined to judge)0.0100.004

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 head0.038
GPT teacher head0.342
Teacher spread0.305 · 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.

Study designSystematic review
DomainMethods
GenreReview

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

Citations81
Published2023
Admission routes2
Has abstractyes

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