Genetic regulation of cell type-specific chromatin accessibility shapes immune function and disease risk

Understanding how genetic variation influences gene regulation at the single-cell level is crucial for elucidating the mechanisms underlying complex diseases. However, limited large-scale single-cell multi-omics data have constrained our understanding of the regulatory pathways linking variants to cell type-specific gene expression. Here we present chromatin accessibility profiles from 3.5 million peripheral blood mononuclear cells (PBMCs) across 1,042 donors, generated using single-cell ATAC-seq, including [~]100,000 PBMCs from 90 donors using multiome (RNA+ATAC) sequencing, with matched whole-genome sequencing. We identified 440,996 chromatin peaks across 28 immune cell types and mapped 24