The recent WTCCC CNV study concluded that common CNVs that can be typed on existing platforms are unlikely to have a major role in the genetic basis of complex diseases [8]. The same study reported that there was no enrichment of association signals among CNVs involving exonic deletions. Our findings recommend caution in assessments of the contribution of CNVs to the genetics of complex traits. Even under the assumption that most common CNVs are well tagged by SNPs and therefore interrogated by existing SNP GWAS, reproducible trait associations are enriched for these CNVs compared to random expectation. The prominence of such CNVs among reproducible trait associations with autoimmune disorders and metabolic traits suggests that these variants may indeed contribute to certain disease classes; alternatively, they may act in conjunction with other variants such as SNPs to confer susceptibility. Importantly, these CNVs are disproportionately more likely to predict transcript levels than frequency-matched SNPs, and they are more likely to affect many different gene expression traits as master regulatory polymorphisms. An important issue to address is whether the enrichment of tCNVs as
