Shared genetic associations and etiology between obstructive sleep apnea and CVDs: A genome-wide cross-trait analysis and bidirectional Mendelian randomization analysis.

Abstract

To investigate the genetic correlations and potential causal relationships between obstructive sleep apnea (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. Utilizing genome-wide association study (GWAS) data, we analyzed shared genetics between OSA and CVDs using linkage disequilibrium score regression (LDSC), multi-trait analysis of GWAS (MTAG), and genotype-tissue expression analysis (GTEx TSEA). We further investigated causal relationships using Bayesian colocalization tests, bidirectional Mendelian randomization (MR), and latent causal variable (LCV) 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 SNPs 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. MR analysis indicated a significant causal effect of OSA on HF and AF as a causal factor for OSA. LCV analysis suggested that AF was causally associated with OSA, while HF showed partial causality. 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.