Fig. 2
Excess of dURVs in non-58EE/DEE genes in individuals with or without pathogenic mutations. a Result of logistic regression analysis testing association between each type of URVs in genes not included in 58EE/DEE genes (non-58EE/DEE genes) and the case−control status. Odds ratios for one additional URV and 95% confidence intervals are plotted. Uncorrected P values for each test are shown beside the plots. Plots are color-coded as shown in the legend of Fig. 1. The combined group of damaging (null and CD missense) URVs (dURVs) was indicated by the purple diamond. b−d Results of analyses of URVs in non-58EE/DEE genes comparing control subjects with the following subsets of case group: cases not carrying dURVs in 58EE/DEE genes (b, n = 605), cases carrying dURVs in 58EE/DEE genes (c, n = 138), and cases carrying convincingly pathogenic URVs (pURVs; e.g. confirmed de novo mutations in 58EE/DEE genes; see the main text and Methods) (d, n = 116). e, f Results of analyses stratifying cases with pURVs in 58EE/DEE genes into subsets. In (e), groups of null pURV carriers (n = 45) and CD missense pURV carriers (n = 71) were analyzed for the burden of dURVs in non-58EE/DEE genes. In (f), we analyzed groups of individuals carrying; pURVs previously reported in non-EE/DEE phenotypes (n = 10, based on information in the Human Gene Mutation Database), pURVs previously reported in EE/DEE (n = 33), and the other pURVs with no or uncertain previous report (n = 73). In (a−f), genes of interest included in the analysis are indicated in the blue boxes (as in Fig. 1), and the case subsets contrasted with the controls are indicated in the light green boxes. The number of URVs analyzed in each test is indicated in the brackets. Statistically significant results considering the total number of hypotheses tested in Figs. 1 and 2 (n = 66) are indicated as follows: **Bonferroni-corrected P < 0.05 (raw P < 0.000758), *Benjamini−Hochberg-corrected P < 0.05 (raw P < ~0.02). g A diagram indicating relationship among the case subsets subjected to the analyses
