Brain vascular and immune single-cell multiomics elucidates disease risk associations

Cerebrovascular dysfunction is implicated in diverse neurological disorders, but how genetic variation in brain vascular, perivascular, and immune cell types may contribute to disease risk remains poorly understood. This gap arises in part because while genome-wide association studies (GWAS) have identified numerous noncoding variants linked to neurological diseases, their cell type-specific effects and target genes in the human brain vasculature remain largely unknown. To address this, we developed a multiomic vessel isolation and nuclei extraction for sequencing (MultiVINE-seq) approach to profile the paired transcriptomes and epigenomes of human brain vascular cells across 30 individuals with varying cognitive statuses.