Two-sample Mendelian randomization analysis unveils a potential genetic association between rheumatic diseases and the risk of idiopathic pulmonary fibrosis

This study aims to elucidate the genetically causal link between rheumatic diseases and idiopathic pulmonary fibrosis (IPF) using Mendelian randomization (MR) analysis. Genome-wide association studies data for IPF were sourced from the FINN cohort in the IEU database, rheumatoid arthritis (RA), systemic lupus erythematosus data, and Sjögren syndrome data from the European Bioinformatics Institute, and ankylosing spondylitis data from Risteys FinnGen. We utilized single-nucleotide polymorphisms as instrumental variables using two-sample bidirectional MR analysis, which included MR-Egger, weighted median, weighted mode, and the inverse-variance weighting method. Sensitivity analysis involved various methods. Bidirectional MR analysis revealed suggestive evidence of an association between RA and IPF. After removal of outliers, the forward MR analysis showed a potential causal effect of RA on IPF using inverse-variance weighting (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.09-1.42) and weighted median methods (OR = 1.27, 95% CI = 1.04-1.55), while MR-Egger and weighted mode analyses did not reach statistical significance. In addition, IPF was identified as a potential risk factor for RA (OR = 1.04, 95% CI = 1.01-1.07) and Sjögren syndrome (OR = 1.23, 95% CI = 1.02-1.49). However, none of the observed associations remained significant after false discovery rate correction for multiple testing. Our analysis yields suggestive evidence of a potential genetic association between rheumatic diseases and IPF, highlighting the need for further investigation into the complex interplay between these conditions.