Fig. 1

An overview of the three components of this study. We probed the effects of individual genes in the 16p11.2 and 22q11.2 CNVs on phenotype in two ways. First (bottom left), we used large GWAS datasets for brain-related traits associated with both CNVs to determine whether variation in predicted expression in any of the individual genes in each CNV was associated with case-control status for each trait. In the second component of this study (top right), we used a biobank containing clinical and genotypic data to identify the individuals with 16p11.2 and 22q11.2 duplications or deletions and determined the clinical traits that were over-represented in CNV carriers. Third (bottom right), we used the biobank to perform a phenome-wide association study to determine clinical traits that are driven by the predicted expression of individual CNV genes, as well as whether these traits overlapped with traits over-represented in CNV carriers. Analyses 1 and 3 are integrated in their use of imputed expression; analyses 2 and 3 are integrated in their use of electronic health data