ArticleBlood advances2025
Multipopulation GWAS for venous thromboembolism identifies novel loci followed by experimental validation in zebrafish.
Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies.iScience · 2023Review
- Meta-analysis fine-mapping is often miscalibrated at single-variant resolution.Cell genomics · 2022Article
- Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases.Cell genomics · 2022Article
- A practical guideline of genomics-driven drug discovery in the era of global biobank meta-analysis.Cell genomics · 2022Article
- Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.Cell genomics · 2022Article
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Authors and funding
22 authors.
Funding
Abstract
abstractVenous thromboembolisms (VTEs) are a leading cause of morbidity and mortality. Although many genetic risk factors have been identified, a substantial portion of the heritability remains unexplained. In this study, we employed a genome-wide association study (GWAS) for VTE across 9 international cohorts of the Global Biobank Meta-Analysis Initiative to address this question, along with in vivo functional validation. In this multipopulation GWAS (VTE cases, 27 987; controls, 1 035 290), 38 genome-wide significant loci were identified, 4 of which were potentially novel. For each autosomal locus, we performed gene prioritization using 7 independent, yet converging, lines of evidence. Through prioritization, we identified genes associated with VTE through GWAS and/or functional studies (eg, F5, F11, VWF, STAB2, PLCG2, TC2N), functionally validated those that did not have evidence other than GWAS (TC2N, TSPAN15), and discovered 1 not previously associated with coagulation (RASIP1). We evaluated the function of 6 prioritized genes with strong genetic evidence, including F7 as a positive control, using laser-mediated endothelial injury to induce thrombosis in zebrafish after CRISPR/Cas9 knockdown. From this assay, we have supportive evidence for the role of RASIP1 and TC2N in the modification of human VTE and suggestive evidence for STAB2 and TSPAN15. This study expands on the currently identified genomic architecture of VTE through biobank-based, multipopulation GWASs, in silico candidate gene predictions, and in vivo functional follow-up of candidate genes.
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Registered trials
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