Shared genetic associations and aetiology between obstructive sleep apnoea and cardiovascular diseases: a genome-wide cross-trait analysis and bidirectional Mendelian randomization analysis.

Abstract

Aims: Study aimed to investigate the genetic correlations and potential causal relationships between obstructive sleep apnoea (OSA) and various cardiovascular diseases (CVDs), aiming to enhance understanding of shared genetic mechanisms and improve recognition and treatment of OSA in patients with CVDs.

Methods and results: Utilizing genome-wide association study (GWAS) data, we analysed shared genetics between OSA and CVDs using linkage disequilibrium score regression, multi-trait analysis of GWAS (MTAG), and genotype-tissue expression analysis. We further investigated causal relationships using Bayesian co-localization tests, bidirectional Mendelian randomization, and latent causal variable analysis. We found strong associations between OSA and multiple CVDs: coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and atrial fibrillation (AF). Novel single-nucleotide polymorphisms related to CVDs were identified during single-trait MTAG analysis. By applying cross-trait MTAG, we identified 15 shared loci between OSA and CAD, 25 shared loci between OSA and MI, and 7 shared loci between OSA and HF. Shared genes are primarily expressed in the blood, heart, kidney, liver, muscle, and pancreas. Mendelian randomization analysis indicated a significant causal effect of OSA on HF and AF as a causal factor for OSA. Latent causal variable analysis suggested that AF was causally associated with OSA, while HF showed partial causality.

Conclusion: Our study suggests strong genetic correlations between OSA and several CVDs. Further research is needed on the associations between OSA and CVDs, as well as the mechanisms of the identified loci.

Lay summary: This study explores the genetic links between obstructive sleep apnoea (OSA) and cardiovascular diseases (CVDs).Key findings are as follows:Strong genetic correlations were found between OSA and five CVDs: coronary artery disease, heart failure (HF), myocardial infarction, stroke, and atrial fibrillation. Novel correlated and causal loci were identified.Atrial fibrillation was identified as a causal factor for OSA, while OSA was a causal factor for HF.Future research is needed to explore these genetic mechanisms further and improve understanding of the connections between OSA and CVDs.