Identifying the genetic link between type 1 diabetes and autoimmune liver diseases.

Abstract

Introduction: It appears that type 1 diabetes mellitus (T1DM) and autoimmune liver diseases (AILDs) are associated, but there is no evidence linking them causally or in a specific direction. This study aims to evaluate the causal relationship between T1DM and AILDs.

Material and methods: We performed a two-sample Mendelian randomization (MR) analysis. Following thorough evaluation, the dataset from the genome-wide association study was utilized to identify potential candidate single nucleotide polymorphisms. Inverse variance weighting (IVW) served as the primary analytical method, complemented by four sensitivity analysis approaches to evaluate result robustness.

Results: Mendelian randomization analysis demonstrated a significant positive causal association between genetically elevated risk of T1DM and autoimmune hepatitis (AIH) (OR = 1.168, 95% CI: 1.060-1.287, p = 0.001), primary biliary cholangitis (PBC) (OR = 1.186, 95% CI: 1.050-1.341, p = 0.006), as well as primary sclerosing cholangitis (PSC) (OR = 1.291, 95% CI: 1.016-1.642, p = 0.037). MR-Egger regression analysis suggested a potential influence of horizontal pleiotropy on the causal association for these conditions (AIH: intercept = -0.026, p = 0.451; PBC: intercept = 0.014, p = 0.745; PSC: intercept = -0.013, p = 0.862). Sensitivity analysis utilizing the leave-one-out method supported the robustness of the Mendelian randomization findings. Conversely, reverse Mendelian randomization analysis revealed that genetically predisposed PBC also raises the likelihood of developing T1DM (OR = 1.236, 95% CI: 1.085-1.407, p = 0.001). Conversely, no causal association was found between AIH and T1DM (OR = 1.032, 95% CI: 0.983-1.084, p = 0.207) or between PSC and T1DM (OR = 0.989, 95% CI: 0.849-1.152, p = 0.888).

Conclusions: Employing two-sample MR analysis, we explored the association between T1DM and AILDs, finding that T1DM elevates the risk of AIH, PBC, and PSC. Further elucidation of the genomic landscape of T1DM and AILDs necessitates large-scale cross-disease genome-wide association studies (GWAS).