Chunk #56 — Methods — SNP and gene findings in the context of previous analyses — Overlap of previous rare coding variants in OCD and GWAS gene-findings
First, we comprehensively assessed the overlap between 251 genes that we highlighted in our manuscript as carrying common risk variation for OCD (Supplementary Table 14), and current gene-based summary statistics from OCD exome sequencing data. We utilized data from Halvorsen et al.88 since it is the largest published exome sequencing study of OCD presently. The supplemental materials from that paper include de novo variant calls from 771 case trios and 1,911 controls (Table S14 in Halvorsen et al.88). We compared the burden of de novo variants, partitioned by variant annotation (synonymous, missense, loss of function) in trio cases versus trio controls within these 251 GWAS-prioritized genes. As was done in the Halvorsen et al.88, we only included de novo variants that were in loci well-covered in both case and control data (In_Jointly_Covered_Loci==TRUE). We also excluded all calls from quartet samples in Halvorsen et al. (Cohort!=“OCD_JHU_quartets”). For each of the four variant annotation classes, we compared the proportion of cases that have at least one qualifying de novo variant to the proportion of controls using a two-sided Fisher’s exact test.
