2- and 3- class CNVs that passed QC and had MAF>10%, the study found that nearly 80% were tagged by SNPs at r2>0.80. Consequently, replication of association results for CNVs can be conducted in an independent sample set by the use of tag SNPs. In this study, we set out to conduct a study of CNVs by analyzing their effect on gene expression and their association with disease susceptibility and other traits. The CNVs that are well-tagged by SNPs, which we call tCNVs, facilitate SNP-based simulation studies to evaluate enrichment. We proceeded to test whether these CNVs were disproportionately more likely to be functional than frequency-matched SNPs, as trait-associated loci or, under the assumption that few trait-associated polymorphisms are likely to alter the composition of gene products, as eQTLs influencing phenotype by altering gene regulation. Our study found that CNV-tagging SNPs are enriched for cis eQTLs, and, furthermore, that reproducible trait associations show an overrepresentation of tCNVs relative to frequency-matched SNPs. While the tagged CNVs are particularly easy to investigate in enrichment studies, we found that the proportion of eQTLs (at p value threshold of 10−4) in the non-WTCCC CNVs (39%) is higher than in the well-tagged WTCCC CNVs (30%).
