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BACKGROUND: African 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. METHODS: Cases 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. RESULTS: We 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. CONCLUSIONS: Our 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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Accidente Cerebrovascular Isquémico , MicroARNs , Accidente Cerebrovascular , Adulto , Humanos , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular Isquémico/complicaciones , Predisposición Genética a la Enfermedad , Accidente Cerebrovascular/genética , Genómica , Polimorfismo de Nucleótido Simple , ADN , Estudios Multicéntricos como AsuntoRESUMEN
The prevalence of hypertension, the commonest risk factor for preventable disability and premature deaths, is rapidly increasing in Africa. The African Control of Hypertension through Innovative Epidemiology, and a Vibrant Ecosystem [ACHIEVE] conference was convened to discuss and initiate the co-implementation of the strategic solutions to tame this burden toward achieving a target of 80% for awareness, treatment, and control by the year 2030. Experts, including the academia, policymakers, patients, the WHO, and representatives of various hypertension and cardiology societies generated a 12-item communique for implementation by the stakeholders of the ACHIEVE ecosystem at the continental, national, sub-national, and local (primary) healthcare levels.
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Hipertensión , Humanos , África/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/prevención & control , PrevalenciaRESUMEN
BACKGROUND: The dietary factors associated with the high burden of hypertension among indigenous Africans remain poorly understood. We assessed the relationship between dietary patterns and hypertension among indigenous Africans. METHOD: In this study, 1550 participants with hypertension matched (for age:â±â5 years, sex and ethnicity) with 1550 participants without hypertension were identified from the stroke-free population in the Stroke Investigative Research and Educational Network study in Ghana and Nigeria. Food consumption was assessed using a food frequency questionnaire, and dietary information was summarized using principal component analysis to identify seven dietary patterns. Conditional logistic regression was applied to compute the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension by tertiles of dietary patterns adjusting for age, education, income, smoking, alcohol use, physical inactivity, family history of cardiovascular diseases, obesity and salt intake at a two-sided P less than 0.05. RESULTS: Multivariable-adjusted OR [95% confidence interval (CI)] for risk of hypertension by second and third tertiles [using the lowest (first) tertile as reference] of dietary patterns were 0.62 (0.48-0.80), 0.70 (0.54-0.90) for whole grains and fruit drinks; 0.87 (0.68-1.12), 0.83 (0.64-1.08) for fruits; 0.85 (0.65-1.10), 0.97 (0.75-1.26) for vegetables, legumes and potatoes; 0.78 (0.60-1.00), 0.84 (0.65-1.08) for fried foods and sweetened drinks; 1.13 (0.88-1.45), 0.80 (0.62-1.03) for poultry product and organ meat; 1.11 (0.86-1.43), 0.88 (0.68-1.14) for red meat; and 1.14 (0.88-1.48), 1.09 (0.84-1.43) for processed foods ( P â<â0.05). CONCLUSION: A higher adherence to dietary consumption of whole grains and fruits was inversely associated with low odds of hypertension in this population.
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Hipertensión , Accidente Cerebrovascular , Humanos , Patrones Dietéticos , Dieta/efectos adversos , Verduras , Frutas , Accidente Cerebrovascular/epidemiología , Hipertensión/epidemiología , Conducta Alimentaria , Factores de RiesgoRESUMEN
Background: The relationship between diagnosed high blood pressure (HBP) and proximity to health facilities and noise sources is poorly understood. We investigated the relationship between proximity to noise sources, sociodemographic and economic factors, and diagnosed HBP in Ibadan, Nigeria. Methods: We investigated 13,531 adults from the African Rigorous Innovative Stroke Epidemiological Surveillance (ARISES) study in Ibadan. Using a Geographic Information System (GIS), the locations of healthcare facilities, pharmaceutical shops, bus stops, churches, and mosques were buffered at 100m intervals, and coordinates of persons diagnosed with HBP were overlaid on the buffered features. The number of persons with diagnosed HBP living at every 100m interval was estimated. Gender, occupation, marital status, educational status, type of housing, age, and income were used as predictor variables. Analysis was conducted using Spearman rank correlation and binary logistic regression at p<0.05. Results: There was a significant inverse relationship between the number of persons diagnosed with HBP and distance from pharmaceutical shops (r=-0.818), churches (r=-0.818), mosques (r=-0.893) and major roads (r=-0.667). The odds of diagnosed HBP were higher among the unemployed (AOR=1.58, 95% CI: 1.11-2.24), currently married (AOR=1.45, CI: 1.11-1.89), and previously married (1.75, CI: 1.29-2.38). The odds of diagnosed HBP increased with educational level and age group. Conclusion: Proximity to noise sources, being unemployed and educational level were associated with diagnosed HBP. Reduction in noise generation, transmission, and exposure could reduce the burden of hypertension in urban settings.