Using data from previously published studies of whole-genome gene expression and genome-wide genotyping,25–29 we assessed whether variants at associated loci (identified as described in the Statistical analysis) regulate levels of mRNA. These expression quantitative trait loci (eQTL) studies included non-tumour lung tissue, blood, and, for variants associated with smoking behaviour, brain. For genes close to peaks of novel signals or genes implicated through eQTL, we assessed differential expression in the lungs of individuals with and without COPD and differential expression in the pseudoglandular and canalicular stages of development of the fetal lung.30,31 Additionally, we generated RNA sequencing data to discover novel transcripts of these genes in human bronchial epithelial cells. We tested all genome-wide meta-analysis p values for enrichment in biological pathways defined in publicly available databases. All functional analyses are described in detail in the appendix (pp 21–23).
