At an expression p value threshold of 10−4, tCNVs from the recently released study (N = 3,432) of CNVs in 16,000 cases and 3,000 controls [8] were evaluated for their effect on gene expression. We first considered tCNVs that are tagged at r2≥0.80. The tag SNPs for these CNVs enable SNP-based analyses and simulation studies. We identified 1,714 such SNPs tagging CNVs (corresponding to 1,761 tCNVs), of which 532 are eQTLs at this threshold; collectively, these SNPs tagging CNVs were found to target 2,215 distinct transcripts. Restricting our focus to eQTLs that regulate transcript levels in cis (defined as within 4 MB of target transcript), we observed a highly significant cis eQTL enrichment (p<0.001) from a simulation procedure (N = 1000) used to empirically generate the null distribution using randomly generated sets of variants of the same set size and matching minor allele frequency distribution as the SNPs tagging CNVs (see Materials and Methods). These SNPs tagging CNVs are significantly more likely to be associated with altered expression of genes in their vicinity than frequency-matched SNPs (see Figure 1). Specifically,
