Human Lung DNA Methylation Quantitative Trait Loci Colocalize with Chronic Obstructive Pulmonary Disease Genome-Wide Association Loci.

Rationale: As the third leading cause of death in the United States, the impact of chronic obstructive pulmonary disease (COPD) makes identification of its molecular mechanisms of great importance. Genome-wide association studies (GWASs) have identified multiple genomic regions associated with COPD. However, genetic variation only explains a small fraction of the susceptibility to COPD, and sub–genome-wide significant loci may play a role in pathogenesis.Objectives: Regulatory annotation with epigenetic evidence may give priority for further investigation, particularly for GWAS associations in noncoding regions. We performed integrative genomics analyses using DNA methylation profiling and genome-wide SNP genotyping from lung tissue samples from 90 subjects with COPD and 36 control subjects.Methods: We performed methylation quantitative trait loci (mQTL) analyses, testing for SNPs associated with percent DNA methylation and assessed the colocalization of these results with previous COPD GWAS findings usin...