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Modulators of Stroke Recovery

The mechanisms influencing recovery after stroke are poorly understood. Higher cognitive reserve (with its proxies educational attainment and intelligence) and brain volume may have a positive impact on neural repair, relearning and compensatory strategies after stroke.

Aims

To assess whether genetic variables modulating cognitive reserve (educational attainment, brain volume, intelligence), depression and physical activity influence stroke functional outcome.

Depression may negatively influence stroke functional outcome. Increased physical activity has been linked to improved functional outcome after stroke in some, but not all studies (Rist Stroke 2011, Krarup Neurology 2008). Physical activity and cognitive reserve may act in concert to promote better recovery, and recovery may be negatively impacted by depression. 

We will use genetic variants identified in genome-wide association studies that influence brain volume (Elliott, BioRxiv 2018), educational attainment, intelligence and physical activity (through its proxy, grip strength, Willems, Nature Communications 2017) and depression (Wray, Nat Gen 2017). Only SNPS that are not in linkage disequilibrium will be used. 

The GISCOME cohort (Maguire, European Journal of Stroke 2017) will be used to analyze functional outcome as determined using the modified Rankin scale. The primary analysis will focus on good functional outcome (modified Rankin Scale 0-2). Secondary analysis will focus on excellent functional outcome (mRS 0-1). 

We will perform SNP risk factor associations (eg SNP-brain volume) and SNP stroke functional outcome associations. We will first use an inverse-variance weighted method and conduct additional complementary analysis using the weighted median and MR-Egger regression methods and the MR-PRESSO to control for biases due to pleiotropy. 
A Bonferroni correction will be applied to the analyses. 

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