Comprehensive survey of CNVs influencing gene expression in the human brain and its implications for pathophysiology

Copy number variations (CNVs) contribute to neuropsychiatric diseases, which may be partly mediated by their effects on gene expression. However, few studies have assessed the influence of CNVs on gene expression in the brain. The objective was to perform an unbiased comprehensive survey of influence of CNVs on gene expression in human brain tissues. CNV regions (CNVRs) were identified in 72 individuals (23 schizophrenia, 23 bipolar disorder and 26 controls). Significant associations between the CNVRs and gene expression levels were observed for 583 CNVR-expression probe pairs (293 unique eCNVRs and 429 unique transcripts), after corrections for multiple testing and controlling the effect of the number of subjects with CNVRs by label swapping permutations. These CNVRs affecting gene expression (eCNVRs) were significantly enriched for rare/low frequency (p = 1.087 × 10−10) and gene-harboring CNVRs (p = 1.4 × 10−6). Transcripts overlapping CNVRs were significantly enriched for glutathione metabolism and oxidative stress only for cases but not for controls. Moreover, 72 (24.6%) of eCNVRs were located within the chromosomal aberration regions implicated in psychiatric-disorders: 16p11.2, 1q21.1, 22q11.2, 3q29, 15q11.2, 17q12 and 16p13.1. These results shed light on the mechanism of how CNVs confer a risk for psychiatric disorders.