Genetic liability to frailty in relation to functional outcome after ischemic stroke

Abstract

Background: Frailty appears to be associated with unfavorable prognosis after stroke in observational studies, but the causality remains largely unknown. Aims: The aim of this study is to investigate the potential causal effect of frailty on functional outcome at 3 months after ischemic stroke using the Mendelian randomization (MR) framework. Methods: Genetic instruments for frailty index were identified in a genome-wide association study meta-analysis including 175,226 individuals of European descent. Corresponding genetic association estimates for functional outcome after ischemic stroke at 90 days were taken from the Genetic of Ischemic Stroke Functional Outcome (GISCOME) network of 6,021 patients. We performed inverse-variance weighted MR as the main analyses, followed by several alternate methods and sensitivity analyses. Results: In univariable MR, we found evidence that genetically predicted higher frailty index (odds ratio [OR] 5.12; 95% confidence interval [CI] 1.31-20.09; p = 0.019) was associated with worse functional outcome (modified Rankin Scale score ≥ 3) after ischemic stroke. In further multivariable MR adjusting for potential confounding traits including body mass index, C-reactive protein, inflammatory bowel disease, and smoking initiation, the overall patterns between genetic liability to frailty and poor functional outcome status remained. Sensitivity analyses with complementary methods and with model unadjusted for baseline stroke severity (OR 4.19; 95% CI 1.26-13.90; p = 0.019) yielded broadly concordant results. Conclusions: The present MR study suggested a possible causal effect of frailty on poor functional outcome after ischemic stroke. Frailty might represent a potential target for intervention to improve recovery after ischemic stroke.

Causal effects of gut microbiota on the prognosis of ischemic stroke: evidence from a bidirectional two-sample Mendelian randomization study

“…Subsequently, several screening steps mentioned above were implemented. Confounding factors, such as smoking (Zhang et al, 2022 ), migraine (Wang et al, 2023 ), frailty (Cai et al, 2023 ), depression (Gill et al, 2019 ), diabetes (Lau et al, 2019 ), body mass index (BMI), and insomnia (Zhang et al, 2023 ), were determined by reviewing the literature. We manually removed 35 SNPs, and a total of 2038 SNPs from 196 taxa were eventually chosen as IVs ( Supplementary Table S2 ).…”

How genetics is impacting on stroke, thrombolysis for central retinal artery occlusion, and cerebral microinfarcts

“…To investigate this question Cai and colleagues used Mendelian Randomization, and publish their findings in this months International Journal of Stroke (IJS). 9…”

“…They conclude that their results support a causal role for frailty on poor functional outcome after ischemic stroke, and that treating frailty might represent a potential target for intervention to improve stroke recovery. 9…”

“…To investigate this question Cai and colleagues used Mendelian Randomization, and publish their findings in this months International Journal of Stroke (IJS). 9 They identified genetic instruments for frailty in a genome-wide association study meta-analysis including 175,226 individuals of European descent. Corresponding genetic association estimates for functional outcome after ischemic stroke at 90 days were taken from the Genetic of Ischemic Stroke Functional Outcome (GISCOME) network.…”

Editorial: Therapeutic strategies and mechanisms for post-stroke emotional disorders

“…The relationship between emotional disorders and stroke has received increasing attention in recent years. Emotional disorders, such as depression, anxiety, apathy, fatigue, and other neuropsychiatric symptoms, not only affect the onset of stroke ( 2 ) but are also related to the prognosis of stroke outcomes ( 3 ). Post-stroke emotional disorders have significant impacts on the activities of daily living, quality of life, rehabilitation, treatment compliance, and mortality of stroke survivors, which increase the burden on families and society.…”