SynthesisBMC medical genomics2022
The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.
Synthesis in BMC medical genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits.American journal of human genetics · 2025Pooled it
- UnlockingNAR genomics and bioinformatics · 2026Article
- Non-Coding SNPs Regulate Bovine Muscle Satellite Cell Proliferation and Differentiation by ModulatingInternational journal of molecular sciences · 2026Article
- The G→C rs590352 in the Protein-Coding Region of ATXN7L3B Gene Upregulates Its Expression In Vivo.Biochemical genetics · 2026Article
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- Structural variants are enriched in deleterious visible phenotypes inGenome research · 2026Article
- A functional SNP rs12718466 in APOA1 promoter modulates gene expression via interaction with SOX7.The Journal of biological chemistry · 2026Article
- Integrative screening identifies functional variants and VNTRs underlying GWAS signals at the 5p15.33 multi-cancer susceptibility locus.medRxiv : the preprint server for health sciences · 2026Article
- Mechanoepigenetics in musculoskeletal disease.Osteoarthritis and cartilage · 2026Review
- Saturating the eQTL map in Drosophila: Genome-wide patterns of cis and trans regulation of transcriptional variation in outbred populations.Cell genomics · 2025Article
- Genetic variants reshape the mScientific reports · 2025Article
- Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks.Nature genetics · 2025Article
- Gene expression variation across genetically identical individuals predicts reproductive traits.eLife · 2025Article
- The Single Nucleotide Substitution T → A rs2072580 Damages the CREB1 Binding Site in the BidirectionalGenes · 2025Article
- Bayesian estimation of allele-specific expression in the presence of phasing uncertainty.Bioinformatics (Oxford, England) · 2025Article
- AI-powered precision medicine: utilizing genetic risk factor optimization to revolutionize healthcare.NAR genomics and bioinformatics · 2025Review
- Epigenetics and individuality: from concepts to causality across timescales.Nature reviews. Genetics · 2025Review
- Genome-wide allele-specific expression in multi-tissue samples from healthy male baboons reveals the transcriptional complexity of mammals.Cell genomics · 2025Article
- Exon-variant interplay and multi-modal evidence identify endocrine dysregulation in severe psychiatric disorders impacting excitatory neurons.Translational psychiatry · 2025Article
- Enhancer RNA transcription pinpoints functional genetic variants linked to asthma.Nature communications · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe remarkable growth of genome-wide association studies (GWAS) has created a critical need to experimentally validate the disease-associated variants, 90% of which involve non-coding variants.
methodsTo determine how the field is addressing this urgent need, we performed a comprehensive literature review identifying 36,676 articles. These were reduced to 1454 articles through a set of filters using natural language processing and ontology-based text-mining. This was followed by manual curation and cross-referencing against the GWAS catalog, yielding a final set of 286 articles.
resultsWe identified 309 experimentally validated non-coding GWAS variants, regulating 252 genes across 130 human disease traits. These variants covered a variety of regulatory mechanisms. Interestingly, 70% (215/309) acted through cis-regulatory elements, with the remaining through promoters (22%, 70/309) or non-coding RNAs (8%, 24/309). Several validation approaches were utilized in these studies, including gene expression (n = 272), transcription factor binding (n = 175), reporter assays (n = 171), in vivo models (n = 104), genome editing (n = 96) and chromatin interaction (n = 33).
conclusionsThis review of the literature is the first to systematically evaluate the status and the landscape of experimentation being used to validate non-coding GWAS-identified variants. Our results clearly underscore the multifaceted approach needed for experimental validation, have practical implications on variant prioritization and considerations of target gene nomination. While the field has a long way to go to validate the thousands of GWAS associations, we show that progress is being made and provide exemplars of validation studies covering a wide variety of mechanisms, target genes, and disease areas.
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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 OpenQuestion graph.