Gene-based and competitive gene set enrichment analyses were conducted in MAGMA (25) (Supplemental Methods). Gene-based test statistics were derived using association summary statistics for all SNPs assigned to each gene including 50kb flanking regions after accounting for LD. P-values were adjusted with a Bonferroni correction for 18,079 genes genome-wide. Gene-based statistics were then analyzed for tissue expression enrichment in 53 distinct human tissues from 714 donors using GTEx RNA-seq data (26), and Bonferroni correction was applied for 53 tissue types (p=0.05/53=9.4×10−4). Tested gene sets included 107 probable autism spectrum disorder susceptibility genes from exome sequencing studies (27), evolutionarily constrained genes (probability of Loss-of-Function Intolerance (pLI) score >0.9), previously identified constrained genes harboring deleterious rare variants (large CNVs or de novo loss of function mutations) in Tourette syndrome cases (4, 5), and all Gene Ontology terms from MSigDB6.0 (Supplemental Methods). Bonferroni correction was applied for the number of gene sets tested.
