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

## TL;DR

This study shows that primary biliary cholangitis increases the risk of a type of stroke called lacunar stroke, based on genetic evidence.

## Contribution

The study provides causal evidence using Mendelian randomization that PBC is a risk factor for lacunar stroke.

## Key findings

- Genetically predicted PBC was associated with increased lacunar stroke risk (OR = 1.0635, p = 0.0022).
- Results were consistently replicated in two updated PBC datasets.
- Sensitivity analyses confirmed robustness and no significant pleiotropy.

## Abstract

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.

•PBC causally increases risk of lacunar stroke•MR evidence is consistent across multiple GWAS•No horizontal pleiotropy detected in analyses•Supports early stroke prevention in PBC patients

PBC causally increases risk of lacunar stroke

MR evidence is consistent across multiple GWAS

No horizontal pleiotropy detected in analyses

Supports early stroke prevention in PBC patients

Health sciences