Genetic Links and Causal Relationships Between OSA and Cardiovascular Disorders

Overview

This study reveals strong genetic correlations between obstructive sleep apnoea (OSA) and multiple cardiovascular diseases (CVDs), including coronary artery disease, heart failure, myocardial infarction, stroke, and atrial fibrillation. Mendelian randomization analyses indicate that OSA causally contributes to heart failure, while atrial fibrillation acts as a causal factor for OSA.

Background

Cardiovascular diseases are leading causes of global mortality, with significant prevalence and burden worldwide. Obstructive sleep apnoea is increasingly diagnosed and affects a substantial portion of the adult population, often coexisting with CVDs. Although associations between OSA and CVDs are well documented, the genetic basis and causal relationships remain poorly understood. Mendelian randomization and genome-wide association studies provide tools to explore these complex interactions and identify shared genetic loci.

Data Highlights

Key Findings

• Strong genetic correlations exist between OSA and five major CVDs: CAD, HF, MI, stroke, and AF.
• Multi-trait GWAS analysis identified novel single-nucleotide polymorphisms (SNPs) shared between OSA and CVDs.
• Cross-trait MTAG revealed 15 shared loci between OSA and CAD, 25 between OSA and MI, and 7 between OSA and HF.
• Shared genes are predominantly expressed in blood, heart, kidney, liver, muscle, and pancreas tissues.
• Mendelian randomization indicates OSA has a causal effect on heart failure, while atrial fibrillation is causally linked as a factor for OSA.
• Latent causal variable analysis supports atrial fibrillation as causally associated with OSA and partial causality for heart failure.

Clinical Implications

Recognition of the genetic overlap and causal relationships between OSA and cardiovascular diseases underscores the importance of screening for OSA in patients with CVDs, particularly heart failure and atrial fibrillation. Understanding these genetic links may guide personalized treatment strategies and prompt further research into targeted therapies addressing shared pathophysiological mechanisms.

Conclusion

This study highlights significant genetic correlations and causal relationships between OSA and several cardiovascular diseases, advancing understanding of their shared genetic architecture. Further research is essential to elucidate the mechanisms underlying these associations and improve clinical management of patients with coexisting OSA and CVDs.

References

1. Genetic Links and Causal Relationships Between Obstructive Sleep Apnoea and Cardiovascular Disorders: Insights from a Genome-Wide Cross-Trait and Bidirectional Mendelian Randomization Study