ReviewAmerican journal of human genetics2023
eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?
Review in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 4 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Unravelling sex differences in the genetic architecture of anxiety.Psychological medicine · 2026Pooled it
- Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects.Nature genetics · 2025Pooled it
- Better together against genetic heterogeneity: A sex-combined joint main and interaction analysis of 290 quantitative traits in the UK Biobank.PLoS genetics · 2024Pooled it
- Association ofCancer genomics & proteomicsPooled it
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Article
- Modeling rare coding variation on chromosome X provides insight into the genetics and differential sex prevalence of autism spectrum disorder.medRxiv : the preprint server for health sciences · 2026Article
- Best practices for improving alignment and variant calling on human sex chromosomes.American journal of human genetics · 2026Article
- Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling.The Journal of clinical investigation · 2026Article
- Somatic loss of the Y chromosome complements polygenic risk scores for type 2 diabetes risk prediction.Nature medicine · 2026Article
- Genetic regulation across germline and somatic variation on the Y chromosome contributes to type 2 diabetes.Nature medicine · 2026Article
- Genome-Wide Association Studies on the Autosomes and Chromosome X Uncover Genetic Basis of Reproductive Traits in Yorkshire Pigs.Animals : an open access journal from MDPI · 2026Article
- Insights into X-Linked Susceptibility to Parkinson's Disease in the South African Population.medRxiv : the preprint server for health sciences · 2025Article
- X chromosome inactivation across primary human tissues is mostly complete, with significant implications for genetic and clinical studies.BMC genomics · 2025Article
- Sex differences in gene regulation and its impact on cancer incidence.bioRxiv : the preprint server for biology · 2025Article
- Sex-specific associations of gene expression with Alzheimer's disease neuropathology and ante-mortem cognitive performance.Nature communications · 2025Article
- Methodological opportunities in genomic data analysis to advance health equity.Nature reviews. Genetics · 2025Review
- Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling.Nature genetics · 2025Article
- Sex-specific genetics underlie increased chronic pain risk in women: genome-wide association studies from the UK Biobank.British journal of anaesthesia · 2025Article
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
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."
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.