Causal association between rheumatoid arthritis and interstitial lung disease: A two-sample bidirectional Mendelian...

Epidemiological observations suggest a potential causal relationship between rheumatoid arthritis (RA) and interstitial lung disease (ILD), and vice versa. Alternatively, this association could be due to simple co-occurrence of RA and ILD resulting from shared population genetic or environmental risk factors. However, the causal nature of this relationship remains uncertain. This study aims to investigate the genetic causality between RA and ILD. Two-sample bidirectional Mendelian randomization (MR) was employed to test the causal effects of RA on ILD and ILD on RA, utilizing genome-wide association studies for ILD and RA. Data statistics were collected from public data sets. Relevant single nucleotide polymorphisms were selected through quality control steps in the meta-analysis results of genome-wide association studies. Two-sample bidirectional MR analysis was conducted to assess the causal relationship between the 2 conditions. The main MR analyses utilized methods such as inverse variance weighting, weighted median, and MR-Egger regression. Sensitivity analyses, including MR-Egger, leave-one-out, MR pleiotropy tests, and heterogeneity tests, were performed to evaluate heterogeneity and pleiotropy. In the European population, the risk of ILD was found to be increased by RA (odds ratio = 1.272, 95% confidence interval: 1.186-1.363, P < .001). Conversely, ILD was associated with an increased risk of RA (odds ratio = 1.111, 95% confidence interval: 1.008-1.223, P = .033). These findings highlight a potential genetic link between rheumatoid arthritis and interstitial lung disease and may inform future research regarding potential screening strategies in genetically susceptible individuals.