ABSTRACT

Stroke, a debilitating neurological disorder with significant global morbidity and mortality, is the focus of this study. Observational studies are susceptible to confounding and limited generalizability. To mitigate confounding and reverse causation, this study employs Mendelian randomization to establish a causal relationship between modifiable risk factors and stroke. Data from the UK Biobank (n = 461,880) and FinnGen (n = 180,862) cohorts were analyzed, using genetic variants as instrumental variables. The study investigates relationships between stroke risk and genetically predicted exposures such as salad and fruit consumption, cheese intake, coffee, body mass index, maternal smoking, and smoking behavior. A genetically estimated higher intake of salads and fruits was observed to be associated with a decreased risk of stroke in both FinnGen and the UK Biobank (salads: odds ratio [OR] 0.98, 95% confidence interval [CI]: 0.97-0.99, P = .006; fruits: OR 0.98, 95% CI: 0.97-0.99, P = .019). Conversely, both maternal smoking (OR 1.003, 95% CI: 1.001-1.01, P = .006) and smoking behavior (OR 1.04, 95% CI: 1.02-1.06, P < .001) were associated with an increased risk of stroke. Physical activity demonstrated a protective effect (OR 0.994, 95% CI: 0.97-0.998, P = .05). In the FinnGen cohort, similar but more pronounced protective effects were observed for fruit consumption (OR 0.60, 95% CI: 0.45-0.82, P = .04) and physical activity (OR 0.78, 95% CI: 0.62-0.98, P < .05). Additionally, maternal smoking in this population was associated with a substantially increased stroke risk (OR 2.20, 95% CI: 1.27-3.01, P < .001). This study underscores the preventive roles of a healthy diet, smoking cessation, and adopting a healthy lifestyle in mitigating the risks of stroke. Further research is warranted to delve into the mechanisms underlying these risks and protective factors.

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