Genetic prediction of the causal relationship between systemic lupus erythematosus and interstitial lung disease: a two-sample Mendelian randomized study

Abstract

Background Systemic lupus erythematosus (SLE) and interstitial lung disease (ILD) are often associated with clinical practice, and their co-pathogenesis and clinical features have been reported. However, genetic causality between SLE and ILD remains unclear. Methods We searched public genome-wide association study (GWAS) databases for SLE and ILD data, and appropriate single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Inverse-variance weighting (IVW) was used as the main analysis method, and the weighted media and weighted models were supplemented by verification. The Cochran Q test was used to evaluate SNPs heterogeneity. The horizontal pleiotropy of SNPs was tested using the Mendelian randomization (MR) Egger intercept test. Using the method of leave-one-out sensitivity analysis method, we evaluated whether MR is affected by a single SNP. Results IVW results showed that SLE significantly increased the risk of ILD (OR = 1.095, P = 0.023). The results obtained using the other two methods were consistent with the IVW. The MR-PRESSO and MR-Egger intercept tests showed that there was no heterogeneity or horizontal pleiotropy among the IVs. The leave-one-out method confirms the robustness of the results. Conclusion Our results showed a genetic prediction of the causal relationship between SLE and ILD. These results provide a valuable contribution to future clinical research on SLE-ILD.