Prioritizing genes associated with brain disorders by leveraging enhancer-promoter interactions in diverse neural cells and tissues

Prioritizing genes that underlie complex brain disorders poses a considerable challenge. By using the CAGE (Cap Analysis of Gene Expression) read alignment files for 439 human cell and tissue types (including primary cells, tissues and cell lines) from FANTOM5 project, we predicted enhancer-promoter interactions (EPIs) of 439 cell and tissue types in human, and examined their reliability. We found that identified EPIs showed activity specificity and network aggregation in cell and tissue types, and discovered that most neurological disorders exhibit heritability enrichment in neural stem cells and astrocytes, while psychiatric disorders and behavioral-cognitive phenotypes exhibit enrichment in neurons.