Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells

DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on BAL cells. Bronchoscopies were performed in 18 subjects with COPD and 15 control subjects (ex- and current smokers). DNA methylation was measured using the Illumina MethylationEPIC BeadChip Kit, covering more than 850,000 CpGs. Differentially methylated positions (DMPs) were examined for ) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, ) accelerated aging using Horvath's epigenetic clock, ) correlation with gene expression, and ) colocalization with genetic variation. We found 1,155 Bonferroni-significant (