Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis

Background Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an immune response to the inhalation of antigens.  Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic variation may play a role in disease development. Methods In this small-scale study, 24 patients diagnosed with HP were matched with control group who shared the patient’s environment and were exposed to the same HP-associated antigens. Logistic regression was employed to identify Single-Nucleotide Polymorphisms (SNPs) associated with HP. Next genes associated with HP were identified using sequence kernel association test (SKAT) analysis. Last, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Oncology (GO) enrichment analysis were employed to find HP signaling pathways using SNPs coded on genes and on non-coding genes, respectively. Results Given the small sample size, no single SNPs or genes were identified to be significantly associated with HP after adjustment for multiple testing. After P-value adjustment, the KEGG and GO pathway enrichment analysis identified 11 and 20 significant pathways respectively using SNPs coded on genes. Among these pathways, Cell cycle, Proteasome and Base excision repair had previously reported to be associated with lung function.   Conclusion This is the first GWAS study identifying genetic factors associated with HP. Although no significant associations at SNPs/gene level were identified, there were significant pathways that are identified associated with HP which need further investigation in large cohorts.