从人类左心房的联合表达分析中发现的新型功能性心房风险基因和途径
Sojin Youn Wass1, Erik J Offerman2, Han Sun3
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Heart rhythm
|June 17, 2023
概括
研究人员发现了81种与心房动 (AF) 风险相关的新基因. 这些发现强调了细胞应激和重塑是关键因素,表明遗传易感性可能在以后的生活中出现.
科学领域:
- 遗传学 是一个遗传学.
- 心脏病学 心脏病学
- 生物信息学是一种生物信息学.
背景情况:
- 全基因组关联研究 (GWAS) 已经确定了100多个与心房 (AF) 相关的遗传位置.
- 然而,确定特定的因果基因和理解它们的机制仍然是AF研究中的一个重大挑战.
研究的目的:
- 确定涉及AF风险位置的新型因果基因和机制性途径.
- 利用基因表达和协同表达分析,以更深入地了解AF病变的发生.
- 为未来的功能研究和AF相关基因的治疗向创造一个有价值的资源.
主要方法:
- 在人类左心房组织中,确定了接近AF风险变异的候选基因的cis表达定量特征位点 (eQTL).
- 进行同表达分析,以确定每个候选基因的基因合作伙伴.
- 利用权重基因同表达网络分析 (WGCNA) 来识别基因模块和丰富的AF基因.
- 应用发明路径分析 (IPA) 给共同表达伙伴和WGCNA模块,以确定重要的生物路径.
主要成果:
- 在135个位置内发现了166个AF风险单核酸多态 (SNP).
- 发现了81种以前未被注释为AF风险基因的新基因.
- IPA揭示了重要的途径,包括线粒体功能障碍,氧化应激,上皮粘附结合信号传递和Sirtuin信号传递.
- WGCNA确定了64个模块,其中8个显示了候选AF基因的丰富,与细胞损伤,压力,新陈代谢和免疫反应有关.
结论:
- 同表达分析表明细胞应激和重塑在AF发展中的关键作用.
- 提出一种双重风险模型,在这种模型中,当压力因素超过适应能力时,对AF的遗传易感性可能在晚年表现出来.
- 提供一种新的资源,以指导对潜在的因果AF基因的功能性研究.
相关概念视频
01:28Mechanism of Cardiac Arrhythmias
968
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
968
01:26Coronary 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
01:25ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias
51
Arrhythmia is a condition characterized by an irregular heart rhythm, with ECG changes that differ based on its origin and nature. The types of arrhythmias discussed below include atrial, junctional, and ventricular arrhythmias.Atrial ArrhythmiasPremature Atrial Complexes (PACs): PACs are early atrial beats caused by stress, caffeine, alcohol, electrolyte imbalances, hypoxia, hyperthyroidism, or certain medications (e.g., bronchodilators and decongestants). The ECG shows early P waves with an...
51
01:20Extrinsic and Intrinsic Pathways of Hemostasis
8.4K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
8.4K
01:19Electrophysiology of Normal Cardiac Rhythm
6.6K
The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase...
6.6K
01:29Heart Failure II: Pathophysiology
16
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
16