Gene-based analysis identifies four top genes enriched for case-only variants in constrained regions. (a) Genes are plotted according to the number of case-only (y-axis) and control-only (x-axis) variants within a gene and its 5 kb flanking regions from our sequence data. Blue squares denote all the variants and the corresponding axes are shown in blue; red diamonds denote variants in constrained elements only and the corresponding axes are shown in red. Genes that are plotted above the identity line harbor more case-only than control-only variants. (b) A similar analysis excluding DP, the breed used to identify genes for sequencing, shows that the enrichment pattern persists for several genes. (c) The case-only variants in constrained elements, when plotted with gene structure and evolutionary conservation, show clustering in ATXN1 (5’ end). Dimmed bars represent canine variants that failed to lift over onto hg19. The conservation track shows a measure of evolutionary conservation in dog, human, mouse and rat . (d) In each gene, SNPs with the greatest risk allele frequency (AF) difference between OCD-risk and control breeds (y-axis) tend to have lower frequency across all genotyped breeds (y-axis). SNPs are shown as solid circles with vertical lines.