SynthesisGenome medicine2024
Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans.
Synthesis in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Advancing genomic medicine in Nigeria: research progress, clinical translation and policy priorities.Journal of community genetics · 2026Review
- Harnessing data science to control non-communicable diseases in Africa: a systematic review and gap analysis.Communications medicine · 2026Article
- Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine.Neurochemistry international · 2025Review
- Decoding Stroke Etiology: Multi-Omics Advancements in Genetic Mechanisms and Clinical Implication.Brain and behavior · 2025Review
- Epidemiology and future trend predictions of ischemic stroke based on the global burden of disease study 1990-2021.Communications medicine · 2025Article
- Advancing neurogenetics in Africa: past achievements, current developments and shaping the future.Nature reviews. Neurology · 2025Review
- Big data approaches for novel mechanistic insights on sleep and circadian rhythms: a workshop summary.Sleep · 2025Article
- Driving Global Health equity and precision medicine through African genomic data.Human molecular genetics · 2025Article
- Lessons from national biobank projects utilizing whole-genome sequencing for population-scale genomics.Genomics & informatics · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.Stroke · 2024Article
- Development of a prediction model for poor outcomes after thrombolysis in mild non-disabling ischemic stroke.Frontiers in neurologyArticle
- MicroRNAs and Cancer Racial Disparities.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
57 authors at 20 institutions in 6 countries.
Funding
Abstract
backgroundAfrican ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans.
methodsCases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation.
resultsWe observed genome-wide significant (P-value < 5.0E-8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E-6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E-6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E-6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping.
conclusionsOur findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke's risk prediction and development of new targeted interventions to prevent or treat stroke.
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