The causal relationship between C-reactive protein and idiopathic pulmonary fibrosis: A univariate and multivariate Mendelian randomization study

Abstract

Abstract Background This study employs univariate and multivariate Mendelian randomization designs, utilizing publicly available Genome-Wide Association Study (GWAS) data, to assess the causal relationship between C-reactive protein (CRP) and idiopathic pulmonary fibrosis (IPF). Methods We obtained IPF GWAS summary statistics (1028 cases and 196,986 controls) from the FinnGen Consortium (r5) and CRP, BMI, and ever-smoked summary statistics from IEU. The primary approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median and MR-PRESSO methods. Sensitivity analyses, including tests for heterogeneity, horizontal pleiotropy, and leave-one-out analysis, were also conducted. Results Mendelian Randomization (MR) analysis reveals a significant causal effect of genetically predicted CRP on IPF (IVW: OR 1.446, 95%CI 1.128–1.854, P = 0.004). This association remains significant after adjusting for BMI and smoking (OR 1.533, 95%CI 1.194–1.96, P < 0.001; OR 1.432, 95%CI 1.129–1.817, P = 0.003, respectively), with no evidence of heterogeneity or horizontal pleiotropy. Sensitivity analyses confirm the stability and reliability of our findings. Conclusion Our findings support a causal relationship between CRP and IPF, emphasizing the importance of monitoring femoral neck IPF in patients with chronic inflammatory conditions. Further research is needed to validate our conclusions and elucidate the underlying biological mechanisms. These discoveries provide valuable insights into the pathogenesis and potential future therapies for IPF.