Fig. 1: CNV size distribution and association with severe neurological and psychiatric disorders.
A Size distribution of largest CNV/individual in the NFBC (left) and FINRISK (right) cohorts. B Meta-analysis of SNPD association in individuals with high-risk CNVs and matched extreme PRS outliers in the FINRISK and NFBC cohorts (n = 27,948). Overall, high-risk deletions except high pLI gene deletions were associated with SNPDs (Supplementary Fig. 3). We ascertained the disease associations using a logistic regression model, correcting for age (log), sex, PCs 1–10, and year of enrollment. ID was the most enriched phenotype in high-risk CNV carriers, though not significantly associated (OR = 3.9 [95% CI 1.7–8.6], padj = 0.080). In CNV subgroups (Supplementary Fig. 5), ID was associated with DECIPHER CNVs (OR = 11.8 [3.4–40.3], padj = 0.0074) and large deletions (OR = 9.9 [3.4–28.3], padj = 0.0018). CNV associations were overall stronger in NFBC (Supplementary Fig. 7) than FINRISK (Supplementary Fig. 6). Schizophrenia was reported more commonly among carriers of ID gene deletions (OR = 7.3 [1.7–31.0], p = 0.0070) and large deletions (OR = 4.9 [1.7–14], p = 0.0024) than among non-carriers, but these associations were not significant after correcting for multiple testing. If no considerable heterogeneity was observed (see Supplementary Methods), a fixed-effects model was assumed (circles), otherwise a random-effects model (triangles) was used in meta-analysis. The sole association significant after multiple testing (PRSSZ and schizophrenia) is denoted with an asterisk.
