Cohort: Stroke

This sequencing project will help develop new more effective stroke prevention, risk assessment and precision diagnostic strategies for Canadians.

Abstract: More than 62,000 Canadians have a stroke each year. Stroke is the fifth leading cause of death and a leading cause of disability. Survivors often face long-term challenges such as physical disabilities, cognitive impairments and emotional distress. Stroke imposes a substantial economic burden, costing the Canadian economy $3.6 billion annually, including hospital care, rehabilitation and decreased productivity. Early prevention, timely treatment and precision diagnostics can help reduce these impacts. The central goal of this project is to use genomics and multiomics to develop novel, useful and impactful stroke prevention, risk assessment and precision diagnostic strategies for Canadians. The project will assess the genomes of 3,200 Canadian stroke patients, and for 2,000 of these patients, provide a detailed multiomic assessment (transcriptomics, proteomics, metabolomics and epigenetics). This world-leading work builds on existing collaborations with the International Stroke Genetics community. Of note, 2,000 of the stroke patients are already recruited with blood samples ready to be measured. Patients have detailed phenotype data entered and biobanked samples to permit the proposed multiomic evaluation. Our team has world leading expertise in multiomics analysis of stroke, including genomics, transcriptomics, metabolomics, proteomics, bioinformatics and machine learning. Our focused projects will leverage genetic and multiomic data to improve the health of Canadians and reduce the burden of stroke and cerebrovascular disease.

1. Stroke Outcome: We will integrate the genomic and multiomic data with our well phenotyped stroke patients to uncover genetic and molecular pathways involved in brain injury and recovery in stroke. This will provide human relevant drug targets to reduce brain injury and personalized approaches to guide therapies that enhance recovery.
2. Stroke Risk Evaluation: Genetics influences stroke risk, affecting response to vascular risk factors and propensity to thrombosis. Leveraging the full CPHI cohort, we will evaluate a Polygenic Stroke Risk Score (PSRS) in Canadians and identify underrepresented groups in which the PSRS requires refinement. We will show how multiomics can contribute to stroke risk assessment and monitoring stroke risk.
3. Stroke Prevention: Knowing the etiology of a stroke is critical to preventing future stroke. In >30 per cent of patients, stroke etiology remains unknown. We will show how an AI model of the genomic and multiomic data can predict stroke etiology. This will improve the precision of stroke prevention by getting stroke patients the correct treatment for their cause of stroke. Collectively, this work will produce novel therapeutic approaches to treat stroke and identify
   stroke patients at increased risk of stroke in need of precisely tailored interventions.