Jagannathan Ram, Seixas Azizi, St-Jules David, Jagannathan Lakshmanan, Rogers April, Hu Lu, Jean-Louis Girardin, Sevick Mary Ann
Hubert Department of Global Health, Emory Global Diabetes Research Center, Atlanta, GA, USA.
NYU School of Medicine, Department of Population Health, Center for Healthful Behavior Change, New York, NY 10016, USA.
Sleep Disord. 2017;2017:6768323. doi: 10.1155/2017/6768323. Epub 2017 Sep 19.
Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. The objective of this systematic genetic study is to identify "novel" biomarkers for OSA using systems biology approach.
Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO) analyses and candidate genes prioritization were performed using Enrichr tool. Genes pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway Analysis.
In total, we have identified 153 genes. The top 10 pathways associated with OSA include (i) serotonin receptor interaction, (ii) pathways in cancer, (iii) AGE-RAGE signaling in diabetes, (iv) infectious diseases, (v) serotonergic synapse, (vi) inflammatory bowel disease, (vii) HIF-1 signaling pathway, (viii) PI3-AKT signaling pathway, (ix) regulation lipolysis in adipocytes, and (x) rheumatoid arthritis. After removing the overlapping genes, we have identified 23 candidate genes, out of which >30% of the genes were related to the genes involved in the serotonin pathway. Among these 4 serotonin receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA.
This preliminary report identifies several potential candidate genes associated with OSA and also describes the possible regulatory mechanisms.
现有基因生物标志物在阻塞性睡眠呼吸暂停（OSA）诊断中的整体有效性仍不明确。这项系统遗传学研究的目的是使用系统生物学方法识别OSA的“新型”生物标志物。
从PubMed、MEDLINE、Embase搜索引擎和DisGeNET数据库中提取OSA的候选基因。使用Enrichr工具进行基因本体（GO）分析和候选基因优先级排序。提取与前10条通路相关的基因并用于Ingenuity通路分析。
我们总共鉴定出153个基因。与OSA相关的前10条通路包括：（i）血清素受体相互作用，（ii）癌症通路，（iii）糖尿病中的AGE-RAGE信号传导，（iv）传染病，（v）血清素能突触，（vi）炎症性肠病，（vii）HIF-1信号通路，（viii）PI3-AKT信号通路，（ix）脂肪细胞中的脂肪分解调节，以及（x）类风湿性关节炎。去除重叠基因后，我们鉴定出23个候选基因，其中超过30%的基因与血清素通路中的相关基因有关。在这4种血清素受体中，SLC6A4、HTR2C、HTR2A和HTR1B与OSA密切相关。
本初步报告鉴定了几种与OSA相关的潜在候选基因，并描述了可能的调控机制。
