This study has several limitations. The sample size of 131 subjects, though adequate for gene expression analyses, may be underpowered to detect all potential eQTL associations. Therefore, we limited the cis-acting analysis to SNPs within 50 kb from the gene, to limit the multiple testing burden. Based on RNA sequencing data, Pickrell et al. estimate that 90% of eQTL SNPs are within 15 kb of a gene [57]. Previous papers have used a 50 kb limit to define cis-acting eQTLs [6]. Using this method, we were able to replicate published eQTL associations from other tissues and were able to identify a set of significant eQTL SNPs to carry forward for COPD association studies. However, our method would be unable to detect cis-eQTLs located >50 kb from the TSS, such as a SNP in an upstream enhancer or in the 3′ UTR of a large gene. Due to the sample size, we limited our investigation to cis-acting eQTL SNPs, as a full search for trans-acting regulatory SNPs greatly increases the number of tests performed. The literature suggests that sample sizes under 200 subjects may be inadequate to find true trans-eQTLs [58].
