A Bi-directional Mendelian Randomization Study of Idiopathic Pulmonary Fibrosis and Six Diabetes-related Traits

Title:A Bi-directional Mendelian Randomization Study of Idiopathic Pulmonary Fibrosis and Six Diabetes-related Traits

Volume: 33

Author(s): Yi Nie*, Hongmei Li and Haibin Wang

Affiliation:

• Department of Endocrinology, The First Affiliated Hospital of Tsinghua University, Beijing, 100016, P.R. China

Keywords: Mendelian randomization, idiopathic pulmonary fibrosis, diabetes, Bi-directional.

Abstract:

Introduction: The objective of the present study was to explore the bi-directional causal relationship between IPF and diabetes (type 1 diabetes and type 2 diabetes)/ diabetic nephropathy/glycemic traits [fasting glucose and glycated hemoglobin (HbA1c)]/fasting blood insulin through MR analysis.

Methods: A bi-directional two-sample Mendelian randomization (MR) study design was adopted to evaluate the causal relationship between IPF and diabetes (type 1 diabetes and type 2 diabetes), diabetic complications (diabetic nephropathy) and glycemic traits [fasting blood glucose, glycated hemoglobin (HbA1c), fasting insulin] in a European population. Genome-wide association study summary data was obtained. The inverse variance weighted (IVW) method with a fixed-effects model was used to estimate the primary causal effects. The causal effects are represented by reporting odds ratios (OR) and their corresponding 95% confidence intervals (CI). The robustness of results was assessed using the MR-Egger and Weighted Median methods.

Results: In the forward MR analysis, the IVW method revealed a significant causal effect of IPF on type 2 diabetes (OR=1.031, 95% CI: 1.011-1.052). Similar estimates were obtained through the Weighted Median method. However, no significant causal effects were observed on type 1 diabetes, diabetic nephropathy, fasting blood glucose, HbA1c, and fasting insulin, respectively (p>0.05). We performed the reverse MR analysis using similar methods to the forward MR approach. MR analysis only showed a significant causal association of fasting insulin with IPF risk, with an OR of 3.576 (95% CI: 1.958-6.531).

Discussion: Genetically determined IPF was linked to an elevated risk of type 2 diabetes. The inverse MR analysis indicated that there was no causal impact of genetically predicted type 2 diabetes on the IPF risk.

Conclusion: Genetically predicted fasting blood insulin was found to be positively associated with IPF risk.

Cite this article as:

Nie Yi*, Li Hongmei and Wang Haibin, A Bi-directional Mendelian Randomization Study of Idiopathic Pulmonary Fibrosis and Six Diabetes-related Traits, Current Medicinal Chemistry 2026; 33 () . https://dx.doi.org/10.2174/0109298673395716250929111029