孟德尔随机化
混淆
多效性
阻塞性睡眠呼吸暂停
医学
内科学
生物信息学
生理学
遗传学
生物
基因型
基因
遗传变异
表型
作者
Zuanguang Chen,Yilin Yang,Yun Chao Wang,Wen-Kai Yu,Shanshan Li,Mei Yang,Ce Zong,Zi Han Zhou,Hanghang Zhu,Lulu He,Xinyu Li,Changhe Shi,Yusheng Li
出处
期刊:Current Neurovascular Research
[Bentham Science]
日期:2023-10-18
卷期号:20
标识
DOI:10.2174/0115672026266627230921052416
摘要
Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered breathing. Studies have shown that certain changes in metabolism play an important role in the pathophysiology of OSA. However, the causal relationship between these metabolites and OSA remains unclear.We use a mendelian randomization (MR) approach to investigate the causal associations between the genetic liability to metabolites and OSA.We performed a 2-sample inverse-variance weighted mendelian randomization analysis to evaluate the causal effects of genetically determined 486 metabolites on OSA. Multiple sensitivity analyses were performed to assess pleiotropy. We used multivariate mendelian randomization analyses to assess confounding factors and mendelian randomization Bayesian model averaging to rank the significant biomarkers by their genetic evidence. We also conducted a metabolic pathway analysis to identify potential metabolic pathways.We identified 14 known serum metabolites (8 risk factors and 6 protective factors) and 12 unknown serum metabolites associated with OSA. These 14 known metabolites included 8 lipids( 1-arachidonoylglycerophosphoethanolamine, Tetradecanedioate, Epiandrosteronesulfate, Acetylca Glycerol3-phosphate, 3-dehydrocarnitine, Margarate17:0, Docosapentaenoaten3;22:5n3), 3 Aminoacids (Isovalerylcarnitine,3-methyl-2-oxobutyrate,Methionine), 2 Cofactors and vitamins [Bilirubin(E,ZorZ,E),X-11593--O-methylascorbate], 1Carbohydrate(1,6-anhydroglucose). We also identified several metabolic pathways that involved in the pathogenesis of OSA.MR (mendelian randomization) approach was performed to identify 6 protective factors and 12 risk factors for OSA in the present study. 3-Dehydrocarnitine was the most significant risk factors for OSA. Our study also confirmed several significant metabolic pathways that were involved in the pathogenesis of OSA. Valine, leucine and isoleucine biosynthesis metabolic pathways were the most significant metabolic pathways that were involved in the pathogenesis of OSA.
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