Genetic causality between type 1 diabetes and arrhythmia: a two-sample Mendelian randomization study

Abstract

Abstract Background Clinical studies have shown that cardiovascular diseases in patients with type 1 diabetes (T1D) are often atypical or asymptomatic. While diabetic cardiomyopathy has been confirmed, the link between T1D and arrhythmia remains unclear. To infer causality between T1D and arrhythmia at the genetic level, we conducted a Mendelian randomization study through the genetic tools of T1D. Methods In this study, we used genetic variables and summary statistics from genome-wide association studies (GWAS) of type 1 diabetes (T1D) and arrhythmia. Single nucleotide polymorphisms (SNPs) were selected based on the assumptions of instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary analysis to summarize the causal effects between exposure and outcome. The weighted median and weighted mode methods were used as secondary methods. We tested for horizontal pleiotropy using the MR-Egger method and detected heterogeneity using the Q-test. A leave-one-out sensitivity analysis was performed. Scatter plots, forest plots, and funnel plots were used to visualize the results of the MR analysis. Results In this study, we selected 28 T1D-related SNPs as instrumental variables. The IVW [odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97 − 1.00, P = 0.008], weighted median (OR = 0.98, 95% CI = 0.96 − 0.99, P = 0.009), and weighted mode (OR = 0.98, 95% CI = 0.96 − 0.99, P = 0.018) analysis methods suggested a causal effect of T1D on arrhythmia. The MR-Egger method indicated no horizontal pleiotropy (P = 0.649), and the Q-test showed no heterogeneity (IVW, P = 0.653). Sensitivity analysis indicated that the MR analysis results were robust. Conclusions Our MR analysis revealed a causal association between T1D and the development of arrhythmia, indicating that patients with T1D had a higher risk of arrhythmia.