Objective To investigate the causal effect of coronavirus disease 2019 (COVID-19) on idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data were sourced from the COVID-19 Host Genetics Initiative and published research. We employed: ① linkage disequilibrium score regression to estimate heritability of individual traits and genetic correlations between COVID-19 and IPF; ② multi-trait analysis of GWAS to identify genetic loci associated with COVID-19 and IPF; ③ Mendelian randomization (MR) to assess causal effect of COVID-19 on IPF; ④ colocalization analysis to identify shared causal variants. Results ① Three COVID-19 phenotypes showed significant positive genetic correlations with IPF (P<0.05); ② Multi-trait analysis of GWAS identified loci jointly associated with COVID-19 and IPF; ③ MR indicated that COVID-19 hospitalization may increase IPF risk (P=0.006); ④ Two causal variants were identified: rs12585036 (posterior probability>0.8, mapped to ATP11A) and rs12610495 (posterior probability>0.8, mapped to DPP9). Conclusions COVID-19 hospitalization may increase IPF risk through inflammatory pathways, providing new insights for managing COVID-19-related pulmonary diseases.
Objective To explore the shared genetic structure and causal relationship between respiratory diseases and obstructive sleep apnea (OSA) through comprehensive genetic analysis. Methods In this study, we utilized large-scale genome-wide association studies (GWAS) summary statistics and novel statistical genetic approaches. We incorporated genetic data related to respiratory diseases to align with OSA. We conducted a genome-wide cross-trait analysis to assess genetic correlation, identify shared loci, examine expression-trait associations, and infer causal relationships. Results We found positive genetic correlation between acute upper respiratory infections and OSA (rg=0.435, P=3.47×10?14), acute lower respiratory infections and OSA (rg=0.481, P=4.03×10?5), acute bronchitis and OSA (rg=0.453, P=7.00×10?4), pneumonia and OSA (rg=0.368, P=7.94×10?10), asthma and OSA (rg=0.364, P=2.73×10?19), and COPD and OSA (rg=0.300, P=1.10×10?10). We conducted a cross-trait meta-analysis to identify shared loci between respiratory diseases and OSA. Additionally, we employed summary-based Mendelian randomization (SMR) to predict causal genes associated with both respiratory diseases and OSA. Mendelian randomization (MR) supported the causal roles of pneumonia (IVW OR=1.15; 95%CI 1.02-1.30), asthma (IVW OR=1.05, 95%CI 1.01-1.08) in OSA, while not observe any significant association between other respiratory diseases and the risk of OSA. Conclusions An intrinsic link between respiratory diseases and OSA has been demonstrated. The genetic correlation and causal role of respiratory diseases in OSA emphasize the importance of considering respiratory health in the management of OSA.