Fig. 1

PolyStrat analysis of pooled-targeted-sequencing data. a Venn diagrams showing the number of SNPs annotated as functional and/or conserved by PolyStrat. Each of the four dashed circles represents the 41,504 total high-confidence SNPs detected. Within each circle, SNPs are stratified by their annotations. Each colorful interior circle represents SNPs annotated as exonic (blue), regulatory (green), conserved (red), or diverged (gray) bases. SNPs with multiple annotations are represented by circle overlaps, and SNPs without any of the included annotations are within the white space of the dashed outer circle. b PolyStrat p-values for 608 genes (circles) stratified by the 16 (12 shown) annotation categories tested show that just five genes (NRXN1, HTR2A, LIPH, CTTNBP2, and REEP3) have p-values below the experiment-wide significance threshold after correction for multiple testing (red dashed line). Two moderately associated, OCD-relevant genes discussed in the text are also noted (STRN and CACNA1C). “Evo” (=evolutionary) are SNPs either conserved (“Cons”) or divergent (“Div”). The vast majority of genes tested fail to exceed the significance threshold, with the median p-value for each category shown as a dark black line separating two boxes representing the 25–75% quantile. Notch in boxes shows the 95% confidence interval around median. c p-values for the five genes robustly implicated in animal models of OCD are significantly lower than p-values for the rest of the genes in our sequencing set (603 genes), and this difference increases when just rare variants are tested. The solid horizontal line shows median p-value, the boxed area the 25–75% quantiles, and the vertical black lines extend from the minimum to maximum p-values observed. AF, allele frequency