Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease

Area of Science:

• Genetics
• Pulmonology
• Bioinformatics

Background:

• Chronic obstructive pulmonary disease (COPD) susceptibility is influenced by genetic factors.
• Previous genetic studies primarily focused on common variants, potentially overlooking the role of coding variants in COPD pathogenesis.

Purpose of the Study:

• To identify coding variants associated with COPD susceptibility.
• To investigate the role of common and rare coding variants in the genetic basis of COPD.

Main Methods:

• Exome array analysis of nonsynonymous, splice, and stop variants in five COPD-enriched cohorts.
• Logistic regression for single-variant association testing with minor allele frequency >0.5%.
• Fixed-effects meta-analysis and replication in additional COPD cohorts.

Main Results:

• Identified significant associations with COPD in known loci (CHRNA5, AGER, MMP3, SERPINA1) and a novel exome-wide significant variant (rs181206) in IL27.
• The IL27 variant (rs181206) was associated with differential expression of genes in lung tissue, including TUFM.
• The IL27 locus is also associated with diabetes, inflammatory bowel disease, and obesity.

Conclusions:

• Exome array analysis revealed novel coding variants associated with COPD, including a significant finding in IL27.
• The identified IL27 variant may contribute to COPD pathogenesis by affecting gene expression.
• These findings expand our understanding of the genetic architecture of COPD.