Causal association between common rheumatic diseases and arrhythmia: a Mendelian randomization study

Area of Science:

• Cardiovascular Genetics
• Rheumatology
• Epidemiology

Background:

• Observational studies suggest a link between rheumatic diseases and arrhythmias, but causality remains uncertain due to confounding factors.
• Previous research is limited by potential confounding and reverse causality, necessitating robust methods to establish a causal relationship.
• Genetic evidence offers a powerful approach to investigate the causal links between complex diseases like rheumatic conditions and cardiac arrhythmias.

Purpose of the Study:

• To investigate the potential causal relationships between six common rheumatic diseases and five types of cardiac arrhythmias.
• To utilize Mendelian randomization (MR) analysis to overcome limitations of observational studies and infer causality.
• To provide genetic evidence for the association between specific rheumatic diseases and arrhythmia risks.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design using single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data.
• Utilized inverse variance weighting (IVW), MR-Egger regression, and weighted median methods for robust causal inference.
• Assessed pleiotropy and validated results using MR-PRESSO, MR-Egger regression, leave-one-out analysis, Cochran's Q-test, and funnel plots.

Main Results:

• Found a significant association between genetically predicted rheumatoid arthritis (RA) and an increased risk of right bundle branch block (RBBB) (OR: 1.10).
• Gout showed a significant positive correlation with an augmented risk of RBBB (OR: 1.28).
• Dermatomyositis (DM) exhibited a significant negative association with the risk of atrioventricular block (AVB) (OR: 0.94).

Conclusions:

• Genetically predicted gout and rheumatoid arthritis are associated with an increased incidence of right bundle branch block in European populations.
• Dermatomyositis may be associated with a reduced risk of atrioventricular block.
• Further research is warranted to elucidate the underlying mechanisms and confirm findings across diverse populations, considering potential genetic variability.