Feng Kun, Yang Jinyue, Liu Kai
Master of Medicine, Department of Medical Affairs, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, PR China.
Master of Science, West China Hospital, Sichuan University, Chengdu, PR China.
Eur J Prev Cardiol. 2024 Nov 5. doi: 10.1093/eurjpc/zwae347.
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.
研究阻塞性睡眠呼吸暂停（OSA）与各种心血管疾病（CVD）之间的遗传相关性和潜在因果关系，旨在加深对共享遗传机制的理解，并改善CVD患者中OSA的识别和治疗。
利用全基因组关联研究（GWAS）数据，我们使用连锁不平衡评分回归（LDSC）、GWAS多性状分析（MTAG）和基因型-组织表达分析（GTEx TSEA）分析了OSA和CVD之间的共享遗传学。我们进一步使用贝叶斯共定位检验、双向孟德尔随机化（MR）和潜在因果变量（LCV）分析来研究因果关系。
我们发现OSA与多种CVD之间存在强关联：冠状动脉疾病（CAD）、心力衰竭（HF）、心肌梗死（MI）、中风和心房颤动（AF）。在单性状MTAG分析期间鉴定出与CVD相关的新单核苷酸多态性（SNP）。通过应用跨性状MTAG，我们确定了OSA和CAD之间的15个共享基因座、OSA和MI之间的25个共享基因座以及OSA和HF之间的7个共享基因座。共享基因主要在血液、心脏、肾脏、肝脏、肌肉和胰腺中表达。MR分析表明OSA对HF有显著因果效应，AF是OSA的因果因素。LCV分析表明AF与OSA存在因果关联，而HF显示出部分因果关系。
我们的研究表明OSA与几种CVD之间存在强遗传相关性。需要进一步研究OSA与CVD之间的关联以及所确定基因座的机制。
