Adiposity and domain-specific stroke recovery: A Mendelian randomization study

Introduction: While adiposity is an established risk factor for incident ischemic stroke, its influence on functional recovery after stroke is uncertain. We leveraged Mendelian randomization (MR) to examine the causal effects of body mass index (BMI) and waist-to-hip ratio (WHR) on post-stroke motor, cognitive, and global recovery. Materials and methods: Genetic proxies for BMI and WHR were obtained from a genome-wide association study (GWAS) meta-analysis of the GIANT consortium and the UK Biobank ( n = 806,834). The primary outcomes were longitudinal trajectories of three National Institutes of Health Stroke Scale (NIHSS) measures assessed over a 2-year period: motor function subscores, cognitive performance subscores, and total NIHSS scores (as a measure of global recovery). Genetic associations with these stroke recovery outcomes were obtained from a GWAS conducted within the VISP trial of mild ischemic stroke ( n = 1270). MR effects were estimated using the inverse-variance weighted method. Results: A 1-standard deviation (SD) increase (~4.8 kg/m 2 ) in genetically predicted BMI associated with lower odds of post-stroke motor improvement (OR = 0.37, 95% CI = 0.19-0.72; p = 0.003). Similarly, a genetically predicted increase in BMI was associated with worse cognitive (β = −0.12, 95% CI = −0.21, −0.03; p = 0.009) and global recovery (β = −0.36, 95% CI = −0.59, −0.13; p = 0.002). Associations between genetically predicted WHR and post-stroke recovery were directionally concordant but were not statistically significant ( p > 0.05). Discussions and conclusions: Human genetic evidence suggests that elevated adiposity negatively impacts multiple post-stroke outcomes, including motor function, cognition, and overall recovery. The biological pathways underlying these associations warrant further investigation.