Exploring causal links between multifaceted dietary exposures and stroke subtypes: Results from a two-sample Mendelian randomization analysis

While observational studies have identified a link between dietary factors and the incidence of stroke, whether this association reflects a causal relationship remains poorly defined. For this work, we utilized a two-sample Mendelian randomization (MR) method to investigate the potential causal association between dietary intake and the risk of stroke. Genetic instrumental variables were extracted from the IEU OpenGWAS and GWAS Catalog databases. The inverse variance weighted method was used to calculate the MR estimates, and sensitivity analyses were performed to evaluate the robustness of the results. Dried fruit intake was associated with a reduced risk of stroke (odds ratio [OR] = 0.991, 95% confidence interval [95% CI]: 0.983-0.998, P = .013) and its subtypes, including ischemic stroke (OR = 0.634, 95% CI: 0.417-0.965, P = .034), small-vessel ischemic stroke (OR = 0.381, 95% CI: 0.195-0.743, P = .005), and lacunar stroke (OR = 0.320, 95% CI: 0.149-0.686, P = .003). Oily fish intake exerted a protective effect against stroke (OR = 0.994, 95% CI: 0.988-0.999; P = .016). Non-oily fish intake reduced the risk of lacunar stroke (OR = 0.256, 95% CI: 0.081-0.807, P = .020), and pork intake reduced the risk of intracerebral hemorrhage (OR = 0.169, 95% CI: 0.031-0.930, P = .041). No significant causal associations were found between stroke and the intakes of processed meat, salad/raw vegetables, fresh fruits, beef, cooked vegetables, poultry, lamb/mutton, or coffee. Reverse MR analyses revealed no widespread and robust reverse causal associations; only 2 nominally significant signals were detected, which had poor analytical robustness or negligible clinical relevance and did not affect the core forward causal inferences. This study provides genetic evidence supporting the causal relationships between specific dietary factors (dried fruit, oily fish, nonoily fish, and pork) and stroke risk, which may have implications for dietary guidance and stroke prevention strategies.