COPD and asthma are two separate diseases with different symptoms and etiologies but can coexist in clinical settings. Both COPD and asthma have genetic components contributing to the disease susceptibility, it has been hypothesized that these two illnesses share some common underlying genetic predispositions. This study aimed to describe the overlap between genetic variants that are independently associated with COPD and asthma, then to dissect the cross-phenotype associations to characterize patterns of pleiotropic effects. The COPD and asthma datasets were separately extracted from an aging population consisting of white European subjects from the UK Biobank database. Genome-wide association tests were performed separately with the COPD and asthma data to first investigate significant genetic variants independently associated with each of the two phenotypes. With the GWAS summary statistics, seven significant genetic loci that exhibit potential pleiotropic effects on COPD and asthma on a genome-wide significant level were identified. Lastly, to further characterize the pleiotropic effects, mediation analyses were performed to distinguish if these significant loci act directly on COPD and asthma, or if the cross-phenotype associations were predominately due to mediation through one of the phenotypes. The mediation analysis results suggested that the genetic effects of the pleiotropic loci on COPD were partially mediated by asthma, yet, at the same time these genetic loci also affect COPD and asthma directly and independently. The observed cross-phenotype associations with COPD and asthma could be explained as a combination of biological pleiotropy and incompletely mediated pleiotropy.
展开▼
