We also created 29 annotations to examine the interaction between protein-truncating variant (PTV)–intolerant (PI) genes and human brain cells. PI genes were obtained from the Genome Aggregation Database (gnomAD), and ascertained using the probability of loss-of-function intolerance (pLI) metric. We selected genes with pLI > 0.9, producing a list of 3,063 genes33. Human brain cell gene sets were based on single-nucleus RNA-seq (sNuc-seq) data generated GTEx project brain tissues in the hippocampus and prefrontal cortex34. Excluding sporadic genes and genes with low expression, for the 14 cell types we selected the top 1,600 (~15%) differentially expressed genes in each cell type, which likely cover all genes that are important for a specific cell type. PI × human brain cell gene sets contained the intersection of genes that are PTV-intolerant and each human brain cell gene set. Annotations were created using a 100-kb window and LD information from the European subsample of 1000 Genomes Phase 3.
