Stroke Investigative Research & Educational Network (SIREN)

Principal Investigator:

Scientific Description:

Stroke is the leading cause of neurological hospital admissions and a leading cause of deaths in Africa. Indeed, with an estimated stroke incidence of up to 315/100,000 population, about 6 Africans develop stroke every minute. Up to 3.2 million Africans develop first-incident stroke every year. Moreover, the burden (death and disability) of stroke in Africa is likely to increase substantially over the next few decades due to the ongoing epidemiological transition from the current dominance by infectious conditions and poverty-related diseases. Further compounding this burgeoning pandemic, strokes disproportionally afflict young and middle-aged adults, a vital segment of the population needed to power economic growth in Africa.

Given all of the aforementioned, it is increasingly becoming clear to policy makers and providers in Africa that identifying ways to mitigate the projected rising public health burden of stroke must be a major public health priority. To tame the escalating burden of stroke in Africa, a proper understanding of the risk factors for stroke is essential for formulating preventive strategies. These are critical elements of the stroke quadrangle (research and surveillance network, prevention, acute care services, rehabilitation). The SIREN projects will culminate a better understanding of the genetic and environmental contributions to stroke. It will contribute to the development of capacity for cutting edge genomic research in Africa.

Updated Aims:
Overarching goal:
To unravel the genomic, TransOmic and environmental determinants of occurrence, type, severity and outcome of stroke and cardiovascular traits (among people of African ancestry). We will explore this using our dataset and in comparison with dataset from African Americans and indigenous Africans from H3Africa and other consortia.
Examples of specific objectives include:
To unravel the:

  • Genomic and environmental risk factors/ determinants for stroke (and transient ischemic attacks), stroke type, subtype, severity, and outcome including sex-specific analyses. TransOmics approaches will also be used.
  • Pleiotropic effect determination in stroke
  • Functional genomics and drug target enrichment analysis of stroke genomic determinants
  • Genetic variation/ population structure of sub-populations in the study (Hausa, Nigerian and Ghanaian subpopulations etc)
  • Genomic and environmental determinants of post-stroke outcomes including disability, cognitive impairment, community participation, depression, anxiety, stress, quality of life
  • Genomic and environmental determinants of cardiometabolic traits in stroke cases and stroke-free population (genetics of Hypertension, Diabetes mellitus, Dyslipidemia [including cholesterol, triglycerides, etc], body adiposity, height, weight, smoking, lifestyle, alcohol use, obesity, diet, waist-hip-ratio, atherosclerosis, socioeconomic class, physical activity, air pollution, etc)
  • Genetics and environmental determinants of white matter hyperintensities and other neuroimaging phenotypes (regional and total brain atrophy, lesion size, number and volumes, etc)
  • Genetics and phenomics of cardiac variables (Echocardiographic and electrocardiographic, ECG) and carotid atherosclerosis (intima thickness, plaques, diameters) ultrasonographic variables.
  • Gene-gene and gene-environment interactions in stroke and cardiovascular diseases
  • Genetic risk scores and Risk calculators for Stroke and stroke risk factors and outcome (as well as cardiometabolic traits including those listed in item 6) .
  • Statistical models for predicting stroke occurrence and outcome
  • Biomarkers for stroke , stroke severity, stroke outcome, stroke subtype and cardiometabolic factors (Hypertension, Diabetes mellitus, Dyslipidemia [including cholesterol, triglycerides, etc], body adiposity, height, weight, smoking, lifestyle, alcohol use, obesity, diet, waist-hip-ratio, atherosclerosis, socioeconomic class, physical activity, air pollution, etc)
  • The causal impact of risk factors on stroke, stroke type, subtype, severity and outcome using Mendelian randomization
  • The causal impact of risk factors on stroke-related traits e.g small vessel disease (leukoaraiosis), dementia, cognitive impairment using Mendelian randomization
  • Pharmacogenomics of drugs for stroke treatment and prevention (including antiplatelets, anticoagulants, thrombolytic drugs, etc.

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