Iron status and the risk of idiopathic pulmonary fibrosis: a mendelian randomization study

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung diseases with unknown etiology. Both preclinical researches and clinical samples have shown an association of iron accumulation with a higher risk of IPF and a decline in lung function. Iron status might be a novel target for IPF therapy if a causal relationship exists. Using mendelian randomization, we investigated the putative causal role for iron status in IPF. Methods: Single nucleotide polymorphisms (SNPs) for iron status were identified from a genome-wide association study (GWAS) on 48972 individuals. The outcome data came from a IPF GWAS (1369 cases; 435866 controls) in UK Biobank. We conducted liberal analyses and conservative analyses with inverse variance weighted (IVW) method as the main analyses. We then performed sensitivity analyses including weighted median, ME-Egger and MR-pleiotropy residual sum and outlier, as well as leave-one-out analyses to detect pleiotripy. Results: In the liberal analyses, IPF was associated with lower log-transformed ferritin using IVW method (OR = 0.998, 95% CI = 0.997 - 0.999, p = 0.030). There were no evidence of a link between iron, transferrin, transferrin saturation and the risk of IPF. In the conservative analyses, we found no evidence of association between four biomarkers of iron status and IPF. Sensitivity analyses suggested no pleiotropy detected (all p > 0.05). Conclusion: We provided potential genetic evidences for the causal associations of lower ferritin with increased incidence of IPF. However, the clinical implications of this finding warrant further investigation.