What is the clinical evidence from this study?

Study design: Observational. Population: Ischemic stroke (n=6021). Intervention: Moderate-intensity physical activity. Primary outcome: Functional recovery (Modified Rankin Scale score 0-2 vs 3-6) (OR 4.91, 95% CI 2.13-11.34, p=0.01).

October 10, 2025Open Access

Lifestyle and poststroke recovery: A 2-sample Mendelian randomization analysis

Q: What does this research mean for the field?

Moderate-intensity physical activity and low-calorie diets significantly improve poststroke recovery, whereas sedentary behavior, higher body mass index, smoking, psychological distress, and insomnia impair it. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Moderate-intensity physical activity significantly improved poststroke recovery (OR 4.91), whereas sedentary behavior, higher body mass index, smoking, psychological distress, and insomnia impaired it.

Study Design

Type

Observational (n=6,021)

Randomization

Mendelian randomization

Multicenter

Yes

Structured PICO

Do genetically predicted lifestyle factors (such as physical activity, diet, sleep, and psychological health) improve or impair poststroke functional recovery in ischemic stroke patients?

Population

6,021 ischemic stroke patients of European ancestry, mean age ~65 years, predominantly middle-aged and older adults from the GISCOME consortium.

Intervention

Genetic predisposition to 12 lifestyle-related exposures (sedentary behavior, low/moderate/high-intensity exercise, body mass index, low-calorie diet, coffee intake, smoking, alcohol abstinence, psychological problems, insomnia, household income) instrumented by 11-26 single nucleotide polymorphisms (SNPs).

Comparator

Genetic predisposition to lower levels or absence of the respective lifestyle factors.

Outcome

Poststroke functional recovery assessed using the Modified Rankin Scale (score 0-2 vs 3-6 adjusted for stroke severity).

This Mendelian randomization study provides genetic evidence that moderate physical activity and a low-calorie diet may improve poststroke recovery, whereas sedentary behavior, high BMI, smoking, psychological distress, and insomnia may impair it.

Main Result

Effect estimate: OR 4.91 (95% CI 2.13-11.34)

p-value: p=0.01

Limitations

Findings are based solely on European ancestry data, limiting generalizability to other populations.
Use of summary-level GWAS data prevented subgroup analyses by age, sex, or comorbidities.
Nonlinear or interaction effects could not be explored.
Statistical power may have been limited for exposures with small effect sizes or fewer instrumental SNPs.
Gene-environment interactions and contextual factors such as socioeconomic status or healthcare access were not addressed.

Abstract

Stroke is a leading cause of long-term disability and mortality worldwide. Modifiable lifestyle factors (including physical activity, diet, sleep, and psychological health) may influence poststroke recovery. However, evidence from observational studies is limited by confounding and reverse causation. We conducted a 2-sample Mendelian randomization (MR) analysis to investigate causal associations between 12 lifestyle-related exposures and stroke recovery outcomes. Genetic instruments (11-26 single nucleotide polymorphisms, all F-statistics > 10) were obtained from the MRC-IEU consortium (sample sizes 64,949-461,460), and outcome data were derived from the GISCOME consortium (6021 ischemic stroke patients, mean age ~65 years, predominantly middle-aged and older adults). Harmonization procedures ensured allele alignment, with palindromic and weak instruments removed. Causal estimates were obtained using inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode methods. Sensitivity analyses included heterogeneity tests, MR-PRESSO, and leave-one-out analyses. Sedentary behavior was associated with poorer recovery (IVW odds ratio OR = 0.01, 95% confidence interval CI: 0.01-0.03, P .05), and MR-PRESSO confirmed the robustness of causal estimates. This MR study provides genetic evidence that sedentary behavior, high body mass index, smoking, psychological distress, and insomnia may impair stroke recovery, whereas moderate-intensity physical activity and low-calorie diets may improve recovery. These findings emphasize the importance of integrating lifestyle modification into personalized stroke rehabilitation strategies.

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