Genetic evidence supports primary biliary cholangitis as a risk factor for lacunar stroke.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease, while lacunar stroke is a common cerebrovascular subtype. Understanding potential systemic vascular consequences of PBC is crucial for patient management. Using a two-sample Mendelian randomization (MR) approach, we investigated the causal effect of PBC on lacunar stroke risk. We utilized genetic instruments for PBC from large-scale genome-wide association studies and tested their association with lacunar stroke in independent datasets. In the discovery analysis, genetically predicted PBC was associated with an increased risk of lacunar stroke (odds ratio [OR] = 1.0635, 95% confidence interval [CI]: 1.0224-1.1063; p = 0.0022). This finding was consistently replicated using two updated PBC datasets (OR = 1.0671, p = 0.0014; OR = 1.0548, p = 0.0026). Sensitivity analyses indicated no significant pleiotropy and confirmed result robustness. This genetic evidence suggests PBC is a causal risk factor for lacunar stroke, warranting further investigation and targeted prevention.