We performed tissue and cell-type enrichment analysis aiming to identify relevant tissues and cell types underlying MDD. First, we analyzed GTEx gene expression data (v8) in 27 human tissues after excluding: 1) tissues with less than 100 donors, 2) non-natural tissues (such as cell lines), and 3) testis tissues (expression outlier).73 Second, for the cell-type analysis, we used single-cell RNA sequencing data with over 160K high-quality cells sampled from 19 regions in the entire mouse central nervous system and peripheral nervous system.17 We analyzed these data at the cell-type level, including 39 broad cell types (level 4) and 251 refined cell types (level 5, after filtering cell types with fewer than 20 cells). We considered only protein-coding genes with 1:1 orthology between human and mouse for the calculation of expression specificity. Third, we further evaluated the heritability enrichment using single-nucleus RNA sequencing data of over 3 million high-quality nuclei from around 100 dissections across adult human brain.18 We analyzed this dataset at the cell-type level including 31 superclusters and 461 cell clusters. For all expression datasets, we calculated a metric
