Copy number variants (CNVs) are rare, highly penetrant structural disruptions. SCZD patients have a 1.15-fold increase in CNV burden, but how this translates into illness is unknown. Patient 4 had four CNVs involving genes previously associated with SCZD or bipolar disorder (BD)13,18,19; of these, neuronal expression of NRG3 and GALNT11, but not of CYP2C19 or GABARB2/GABARA6 was affected (SI Fig. 12, SI Table 5). A second analysis of CNVs unbiased by previous GWAS studies identified 42 genes affected by CNVs in our four SCZD patients (SI Table 5). Though twelve of these genes showed altered neuronal expression consistent with genotype (p<0.05), most changes were extremely small and only three (CSMD1, MYH1, MYH4) showed >1.3-fold effects (SI Table 5). Well-established SCZD CNVs occur at 1q21.1, 15q11.2, 15q13.3, 16p11.2 and 22q11.2,13,18,19, but the relevant genes remain unidentified. Our patients had no evidence of CNVs at these regions, and gene expression of the best candidate genes in each region, such as GJA8 (1q21.1), CYFIP1 (15q11.1), CHRFAM7A (15q13.3), PRODH (22q11.2), COMT (22q11.2) and ZDHHC8 (22q11.2)18,20, was not affected in our SCZD hiPSC neurons (SI Table 6).
