CNVs can affect phenotype in several ways [16]. Genes fully covered by CNVs may contribute to disease through a duplication or deletion event. Copy number variant breakpoints may disrupt the expression of genes that overlap CNVs. On the other hand, we have identified two CNVs at considerable distance (in trans) from their targets controlling transcript abundance as potential master regulators. Another CNV contains multiple regulatory elements which are each predicting the expression of at least 80 transcripts; the deletion of such important regulatory elements is likely to profoundly alter gene transcription. Importantly, we observed that 1,306 CNVs (out of the 3,432 CNVs included in the WTCCC study) harbor at least one SNP eQTL (defined at p value threshold of 10−4). Given our earlier observation that tCNVs are enriched for expression-associated CNVs (eCNVs), it is interesting to ask whether those CNVs not well-tagged by SNPs have interesting properties with respect to gene regulation. Of the CNVs that are tagged at r2<0.30, 44% harbor SNP eQTLs.
