C21 MECHANISMS THAT LINK AGING WITH LUNG DISEASE: THE CUTTING EDGE: Integrative Genetic And Gene Expression Networks Reveal Potential Roles For Microrna Isoforms In COPD And Ild

Methods: As part of the Lung Genomics Research Consortium, we sequenced the small RNA in lung tissue samples from subjects with COPD (n= 150) or ILD (n= 149) and from normal lung tissue (n= 65). Reads mapping to a microRNA locus were grouped into those with the canonical seed and those with an alternative seed due to variation in the 5'start position (isomiRs). 253 of these samples were also profiled with gene expression and SNP microarrays.Results: The expression levels of 309 canonical microRNAs and 242 isomiRs were significantly different between patients with disease and controls (FDR< 0.05). Unsupervised clustering of these microRNAs revealed four distinct groups of subjects with distinct clinical and pathological characteristics including groups enriched for COPD subjects, ILD subjects, or an admixture of both ILD and COPD subjects. Separate causality networks linking SNPs with …