Chunk #74 — STAR* METHODS — QUANTIFICATION AND STATISTICAL ANALYSIS — Relationship of Lead SNPs from Meta-analysis to Rare CNVs and Mutations Previously Associated with Neurodevelopmental Genomic Disorders
We also examined overlap of our 146 genomewide significant loci with genes containing damaging de novo (truncating, highly damaging missense and damaging missense) mutations among children with ASD (data from (Satterstrom et al., 2019)). In this autism dataset, 102 genes had higher frequencies of damaging de novo mutations (DNMs) in cases than controls (FDR q ≤ 0.1) (Satterstrom et al., 2019). Each permutation test consisted of randomly sampling 1,000 new sets of genes with replacement from the genome, where each new set of genes contained the same total number of genes as the observed set of candidate genes for each set of loci. Sampling was also performed while controlling for per-gene mutation rates and brain expression levels using a quantile-based binning approach, as has been described in detail in a recent study (Satterstrom, et al., 2019). P-values were derived by comparing the empirically observed number of genes present in the list of 102 dominant-acting ASD risk genes to the distribution of expected count of dominant-acting ASD risk genes based on 1,000 matched permutations (Data S3.2).
