Causal associations of obstructive sleep apnea with cardiovascular disease: a Mendelian randomization study

孟德尔随机化 医学 阻塞性睡眠呼吸暂停 优势比 内科学 心力衰竭 全基因组关联研究 人口 心房颤动 心脏病学 睡眠呼吸暂停 单核苷酸多态性 置信区间 遗传学 基因型 基因 环境卫生 生物 遗传变异
作者
Ye Li,Yuyang Miao,Qiang Zhang
出处
期刊:Sleep [Oxford University Press]
卷期号:46 (3) 被引量:21
标识
DOI:10.1093/sleep/zsac298
摘要

Abstract Study Objectives Obstructive sleep apnea (OSA) had been associated with various cardiovascular diseases (CVDs) in observational studies, but causal inferences have not been confirmed. We used the Mendelian randomization (MR) study to explore the potential causal association between OSA with CVDs in the general population. Methods We performed a two-sample MR analysis using five gene-wide significant single-nucleotide polymorphisms associated with OSA at genome-wide significance from the FinnGen study (N = 217 955) and 12 cardiovascular diseases from the UK Biobank and the genetic consortia. The inverse-variance weight was chosen as the primary analysis and was complemented by various sensitivity analyses. The study design applied univariable MR, multivariable MR, and mediation analysis. Results MR analyses provide evidence of genetically predicted OSA on the risk of heart failure (odds ratio [OR],1.26; 95% confidence interval [CI],1.08 to 1.47), hypertension (OR,1.24; 95%CI, 1.11 to 1.39) and atrial fibrillation (OR,1.21; 95%CI,1.12 to 1.31). Multivariable MR indicated the adverse effect of OSA on heart failure persisted after adjusting BMI, smoking, drinking, and education (IVW OR,1.13; 95%CI, 1.01 to 1.27). However, the significance of hypertension and atrial fibrillation was dampened. Mediation analyses suggest that the causal association between OSA and heart failure is mediated in part by Apolipoprotein B, with a mediated portion of 9%. Conclusions This study suggested that genetically predicted OSA is a potential causal risk factor for heart failure based on a large-scale population. Nevertheless, further studies regarding ancestral diversity are needed to confirm the causal association between OSA and CVDs.
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