Mendelian randomisation highlights type 1 diabetes as a causal determinant of idiopathic pulmonary fibrosis

Abstract

BackgroundIt is unclear whether type 1 diabetes (T1D) causes idiopathic pulmonary fibrosis (IPF), despite observational research linking the two conditions. Therefore, our study aimed to examine the causal link between T1D and the likelihood of IPF by employing the Mendelian randomization (MR) technique of two-sample Mendelian randomization.MethodsUsing data from two genome-wide association studies (GWAS) with European ancestry, we performed a two-sample MR analysis. These studies involved 18,856 individuals (6,683 cases and 12,173 controls) for T1D and 198,014 individuals (10,028 cases and 196,986 controls) for IPF. We utilized inverse-variance weighted (IVW) analysis as our main approach to determine the association between the risk of IPF and T1D. To evaluate multidirectionality, the MR-Egger regression test was utilized, whereas heterogeneity was assessed using Cochran’s Q test. Additionally, a leave-one-out analysis was performed to assess the reliability of the results.Results38 SNPs linked to T1D were employed as instrumental variables (IVs). Multiple MR methods yielded consistent results, and the MR analysis reveals a significant and positive causal impact of T1D on IPF (MR-IVW, odds ratio [OR] = 1.128, 95% confidence interval [CI] 1.034–1.230; P = 0.006). The limitations of the study include the lack of data from non-European groups and the inability to rule out the possibility of small links. Larger MR experiments are necessary to investigate minute impacts.ConclusionsThe results of this study provide evidence that T1D contributes to the onset and advancement of IPF. This finding may provide important insights into the cause of IPF and possible treatments in the future.