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Adiposity and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study
Mengmeng Wang1, Zhizhong Zhang1, Iyas Daghlas1
1From the Department of Neurology (M.W., X.L.), The Third Affiliated Hospital of Soochow University, Changzhou, China; Department of Neurology (Z.Z.), Jinling Hospital, Medical School of Nanjing University, China; Department of Neurology (I.D.), University of California San Francisco; Department of Epidemiology and Biostatistics (D.G.), School of Public Health, St Mary's Hospital, Imperial College London, United Kingdom; and Department of Integrated Traditional Chinese and Western Medicine (D.L.), The Third Affiliated Hospital of Soochow University, Changzhou, China.
Background And Objectives:
To investigate the causal relationships of abdominal adiposity (waist-to-hip ratio [WHR]) and overall adiposity (body mass index [BMI]) with functional outcome after ischemic stroke using Mendelian randomization.
Methods:
Genetic instruments for WHR and BMI were obtained from the largest available genome-wide association studies meta-analysis of the Genetic Investigation of ANthropometric Traits consortium and the UK Biobank (N max = 806,834). Functional outcome after ischemic stroke was assessed using the modified Rankin Scale (mRS) score at 3-month after stroke onset, with mRS >2 (mRS 3-6) defined as an unfavorable functional outcome. Corresponding genetic estimates for an unfavorable functional outcome were extracted from the Genetics of Ischemic Stroke Functional Outcome network (N = 6,021). We applied a random-effects inverse variance weighted method as our main analysis.
Results:
Genetically predicted higher WHR (per 0.09 ratio units) was associated with unfavorable functional outcome after ischemic stroke (mRS 3-6, OR = 1.48; 95% CI = 1.03-2.13; p = 0.033). The results remained directionally consistent in sensitivity analyses. Conversely, genetically predicted BMI (per 4.8 kg/m2) was not associated with unfavorable functional outcome after ischemic stroke (OR = 1.01; 95% CI = 0.75-1.36; p = 0.937).
Discussion:
This study provides genetic evidence supporting the hypothesis that abdominal adiposity has a detrimental effect on functional recovery after ischemic stroke.
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