We also identified 325 duplicated genes (Supplementary Table 12) significantly enriched among the patients (Benjamini-Hochberg corrected p < 0.05). As for deletions, nearly all genes enriched among duplications at this stringent threshold were within known pathogenic duplications and were overrepresented (IPA) in categories that fit well with the expected phenotypic abnormalities (e.g. cardiovascular disease, developmental, endocrine system and developmental disorders). Expanding our analysis to enrichments with nominal significance identified IPA functions identical to the conservative approach as well as several promising candidate gene regions. We observed duplications containing three genes (SH3YL1, ACP1 and FAM150B) on chromosome 2p in cases with craniofacial disorders (p = 0.01032). Notably, large 2p distal duplications have been associated with facial dysmorphism in multiple case reports35,36. Similarly, we observed duplication of two genes (RSPO4 and PSMF1) on distal chromosome 20p in cases with cardiac defects (p = 0.01195), and larger duplications of 20p have been associated with cardiac defects37. The results suggest a potential role for these small subtelomeric regions in disease. Finally, we observed duplication of proximal 8p extending to include two genes in cases with neurological disorders (p = 0.00479), one of which (FNTA) has been shown to be more highly expressed in schizophrenia38.
