Since gene expression is intermediate to other complex phenotypes, a global view of the influence of CNVs on the transcriptome may lead to a better understanding of their role in disease susceptibility. While we identified, as perhaps expected, CNVs located in the HLA region associated with multiple expression phenotypes and with various autoimmune disorders, we also observed, strikingly, several non-HLA CNVs that regulate multiple transcripts, including 2 (one on chromosome 10 and the other on chromosome 2) associated with more than 100 expression traits. Using the most extensive population-based CNV map available [7], we observed a greater proportion of master regulatory CNVs than observed among the well-tagged CNVs. Collectively, all these findings reinforce the importance of considering all types of variation to elucidate the genetic architecture of complex traits.
