Unveiling the Roles of PRDX6 and SLC6A9 in Intracerebral Hemorrhage-Associated White Matter Lesions.

Intracerebral hemorrhage (ICH) is a common cerebrovascular disorder that frequently leads to white matter lesions (WML), resulting in persistent neurological deficits. However, the molecular mechanisms underlying ICH-induced WML remain incompletely understood. In this study, we employed an integrative bioinformatics approach combining two-trait Mendelian randomization (MR) analysis with single-cell RNA sequencing (scRNA-seq) to explore potential genetic contributors to WML following ICH. Based on expression quantitative trait loci (eQTL) data, MR analysis identified PRDX6 as a high-risk gene and SLC6A9 as a potential low-risk gene for WML following ICH. scRNA-seq further suggested cell-type-specific expression patterns of these genes in normal and ICH-affected mouse brain tissues. Functional enrichment analyses, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, indicated that PRDX6 may be involved in antioxidant defense and metabolic processes, whereas SLC6A9 may be associated with transmembrane transport and neuroprotective functions. These findings offer new insights into the pathophysiology of ICH-induced WML and may serve as potential targets for future therapies.