Causal relationship between type I diabetes mellitus and atrial fibrillation: A Mendelian randomization study

Abstract

Background: Patients with type 1 diabetes mellitus have been at heightened risk for developing atrial fibrillation. We aimed to investigate whether this association is causal using Mendelian randomization. Methods: Using publicly available genome-wide association studies data, we selected single nucleotide polymorphisms significantly associated with type 1 diabetes mellitus as instrumental variables. We employed inverse variance-weighted, weighted median, MR-Egger regression, simple mode, and weighted mode methods within a two-sample Mendelian randomization framework to assess the causal relationship between type 1 diabetes mellitus and atrial fibrillation. We evaluated the pleiotropy and heterogeneity levels of the included genetic instruments using MR-PRESSO, MR-Egger intercept test, Cochran’s Q test, funnel plots, and leave-one-out plots. Results: Causal impact of type 1 diabetes mellitus on atrial fibrillation: Inverse variance weighted (odds ratio [OR] = 0.996, 95 % confidence interval [CI]: 0.985–1.007, P = 0.498). MR-Egger (OR = 1.000, 95 % CI: 0.985–1.016, P = 0.963). Weighted median (OR = 0.985, 95 % CI: 0.973–0.998, P = 0.022). Simple mode (OR = 1.007, 95 % CI: 0.974–1.040, P = 0.698). Weighted mode (OR = 0.995, 95 % CI: 0.984–1.005, P = 0.298). MR-Egger intercept test (P = 0.437). There was no evidence of pleiotropy among the genetic instrumental variables included in the analysis. Conclusions: In Mendelian randomization analysis, we did not find evidence of a causal relationship between genetically determined type 1 diabetes mellitus in European ancestry populations and atrial fibrillation.

Keywords

• Type 1 diabetes mellitus
• Atrial fibrillation
• Genome-wide association
• Mendelian randomization