转录组范围的关联研究揭示了冠状动脉样硬化的新型易感基因
Qiuping Zhao1, Rongmei Liu1, Hui Chen1
1Heart Center of Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.
Frontiers in cardiovascular medicine
|June 23, 2023
概括
这项研究使用全转录组关联研究确定了与冠状动脉样硬化相关的新基因,包括NBEAL1. NBEAL1表现出保护作用,并在动脉样硬化斑块内的关键免疫细胞中表达.
科学领域:
- 遗传学 遗传学 是一个
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
背景情况:
- 遗传因素显著影响冠状动脉样硬化发展.
- 全基因组关联研究 (GWAS) 已经确定了许多风险位置,但由于它们的非编码位置,将它们转化为疗法是具有挑战性的.
- 全转录组关联研究 (TWAS) 提供了一种方法,可以从表达数据中识别潜在的致病基因.
研究的目的:
- 使用TWAS. 选潜在的冠状动脉样硬化致病基因.
- 探索与这些基因相关的潜在生物机制.
- 研究已识别的基因的因果关系和细胞类型特异性表达.
主要方法:
- 采用了四种TWAS方法 (PrediXcan,JTI,UTMOST,FUSION) 来识别冠状动脉样硬化相关的基因.
- 使用Metascape和基于总结数据的门德尔随机化 (SMR) 进行了丰富分析,以推断因果关系.
- 在人类冠状动脉单细胞RNA-seq数据中检查了候选基因的细胞类型特异表达.
主要成果:
- 通过至少三种TWAS方法确定了与冠状动脉样硬化相关的19个基因,其中NBEAL1被全部四种方法确定.
- 丰富分析显示,喘和白细胞介导免疫力有显著的丰富.
- SMR分析证实了NBEAL1和冠状动脉样硬化之间的因果保护关系,在巨细胞,血细胞和内皮细胞中具有差异性表达.
结论:
- 确定了新的基因,特别是NBEAL1,与冠状动脉样硬化有关.
- 突出了潜在的生物功能和免疫细胞参与动脉样硬化病变的发生.
- 为进一步研究动脉样硬化治疗点提供了基础.
相关概念视频
Genome-wide Association Studies-GWAS
13.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.6K
Single Nucleotide Polymorphisms-SNPs
15.3K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.3K
Coronary Artery Disease I: Introduction
28
Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
28
Coronary Artery Disease II: Pathophysiology
15
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
15
Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
16
Atherosclerosis is a progressive disorder that leads to the thickening and narrowing of arterial walls due to plaque buildup. This condition can cause various symptoms depending on the arteries affected:Coronary Artery Disease (CAD): This condition affects the coronary arteries and may lead to chest pain (angina), shortness of breath (dyspnea), heart attacks, and other heart disease symptoms.Cerebrovascular Disease: This affects blood flow to the brain, causing transient ischemic attacks (TIAs)...
16
Atherosclerosis I: Introduction
13
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
13


