Causal and shared genetic insights into severe COVID-19 and idiopathic pulmonary fibrosis.

Although the immediate threat of COVID-19 has lessened, survivors of severe disease still face long-term risks. Utilizing publicly available GWAS summary statistics, we conducted PheWAS enrichment across 2,142 phenotypes to ascertain the traits linked to severe COVID-19. Subsequently, we conducted genome-wide cross-trait analyses to explore genetic correlations, pleiotropic loci, and functional annotations. Mendelian randomization (MR) was employed to deduce causality. Idiopathic pulmonary fibrosis (IPF) emerged as a phenotype significantly linked to severe COVID-19 after false discovery rate correction. We identified substantial genetic correlations and 14 shared pleiotropic loci between severe COVID-19 and IPF, encompassing five additional loci that validated nine variants, notably rs34517439. MR and CAUSE analyses substantiated the causal impact of genetic predisposition on IPF in individuals with severe COVID-19. These findings demonstrate a genetic overlap and a causal relationship between IPF and severe COVID-19, enhancing comprehension of the mechanisms and guiding risk stratification and prevention strategies.