Genetic Causality between Type 1 Diabetes and Arrhythmia Identified by a Two-sample Mendelian Randomization Study

Area of Science:

• Cardiovascular Genetics
• Metabolic Disorders
• Epidemiology

Background:

• Cardiovascular diseases in type 1 diabetes (T1D) can be atypical or asymptomatic.
• The genetic relationship between T1D and arrhythmia is not well understood.
• Mendelian randomization (MR) can infer causality using genetic variants.

Purpose of the Study:

• To investigate the causal effect of T1D on arrhythmia using a genetic approach.
• To leverage genome-wide association study (GWAS) data for T1D and arrhythmia.
• To employ MR methods to assess the genetic predisposition to arrhythmia in T1D.

Main Methods:

• Utilized summary statistics from GWAS for T1D and arrhythmia.
• Selected 28 T1D-associated single nucleotide polymorphisms (SNPs) as instrumental variables.
• Applied inverse variance-weighted (IVW), weighted median, and weighted mode methods for causal inference.
• Assessed horizontal pleiotropy and heterogeneity using MR-Egger and Q-test, respectively.
• Performed sensitivity analyses including leave-one-out.

Main Results:

• MR analysis indicated a causal effect of T1D on arrhythmia (IVW OR=0.98, P=0.008).
• Consistent results were observed with weighted median (OR=0.98, P=0.009) and weighted mode (OR=0.98, P=0.018) methods.
• No significant horizontal pleiotropy (MR-Egger P=0.649) or heterogeneity (Q-test P=0.653) was detected.
• Leave-one-out analysis confirmed the robustness of the findings.

Conclusions:

• This MR study provides genetic evidence for a causal association between T1D and an increased risk of developing arrhythmia.
• Findings suggest that individuals with T1D have a genetically influenced higher susceptibility to arrhythmias.
• Highlights the importance of monitoring for arrhythmias in patients with type 1 diabetes.