Fig. 3. Enrichment of rare LoF variants in ASD cases across gene sets.

Gene sets were defined and grouped by transcriptome proteome, neuronal regulome, ASD gene prediction scores, genetic evidence from neuropsychiatric diseases, and gene-level constraint. Analyses were repeated after removing known ASD or NDD genes. (Number of genes in each set before and after removing known genes are shown in parentheses below gene set.) Dots represent fold enrichment of DNVs or odds ratios for overtransmission of LoF variants in each set. Horizontal bars are presented as mean values with 95% confidence interval as error bars. For each gene set, we show the percentage of overtransmission of rare LoFs to cases. Enrichment of rare inherited LoFs was evaluated by the share of overtransmission events (the transmission and nontransmission of ultra-rare LoFs with pExt ≥ 0.1) in the selected gene set vs those in all other constrained genes using a two-by-two table. P values were determined using the χ² test. Exact P values are listed in Supplementary Table 19.