Project description:We investigated genetic background of familial and early onset atrial fibrillation (AF) with the aim of identify genes involved in atrial fibrillation pathology and are highly predisposing risk factors. We performed whole exome sequencing on 24 families where three or more family members suffered from AF.
Project description:Atrial fibrillation (AF) is the most common heart arrhythmia disease. The greatest risk of atrial fibrillation is stroke, and stroke caused by valvular heart disease with atrial fibrillation (AF-VHD) is more serious. the development mechanism from VHD to AF-VHD is not yet clear. The research on expression profiles of lncRNA and mRNA is helpful to explore molecular mechanism in patients with valvular heart disease who develop atrial fibrillation.
Project description:Atrial fibrillation (AF) is the most common persistent arrhythmia that affect 1–2% of the general population. People with AF display an array of complications cardiogenic stroke and systemic embolism caused by hemodynamic instability and blood hypercoagulability in clinical practice. However, it’s still unclear whether and how ubiquitylated proteins react to AF in the left atrial appendage of patients with AF and valvular heart disease. This theory focuses on the changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease. We firstly widely analysis the proteins ubiquitination in patients with atrial fibrillation.
Project description:<p>The Massachusetts General Hospital (MGH) Atrial Fibrillation Study was initiated in 2001. The study has enrolled serial probands, unaffected and affected family members with atrial fibrillation. At enrollment participants undergo a structured interview to systematically capture their past medical history, AF treatments, and family history. An electrocardiogram is performed; the results of an echocardiogram are obtained; and blood samples are obtained.</p> <p>For the TOPMed WGS project only early-onset atrial fibrillation cases were sequenced. Early-onset atrial fibrillation was defined as an age of onset prior to 66 years of age.</p> <p>Comprehensive phenotypic and pedigree data for study participants are available through dbGaP <a href="./study.cgi?study_id=phs001001">phs001001</a>.</p>
Project description:<p>The Massachusetts General Hospital (MGH) Atrial Fibrillation Study was initiated in 2001. The study has enrolled serial probands, unaffected and affected family members with atrial fibrillation. At enrollment participants undergo a structured interview to systematically capture their past medical history, AF treatments, and family history. An electrocardiogram is performed; the results of an echocardiogram are obtained; and blood samples are obtained.</p> <p><b>The Massachusetts General Hospital (MGH) Atrial Fibrillation Study is utilized in the following dbGaP substudies.</b> To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001001 Massachusetts General Hospital (MGH) Atrial Fibrillation Study. <ul> <li><a href="./study.cgi?study_id=phs001116">phs001116</a> MGH AF CHARGE-S</li> <li><a href="./study.cgi?study_id=phs001117">phs001117</a> MGH AF Exome Sequencing</li> <li><a href="./study.cgi?study_id=phs001118">phs001118</a> MGH AF Medical Resequencing</li> </ul> </p>
Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AFï¼which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarrayï¼focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation. We conducted an integrated analysis of myocardial sleeves of pulmonary veinsï¼PVsï¼from 12 patients (6 non-AF and 6AF) in our center, of which hypertension, diabetes, smoking and alcohol abuse were excluded, using a second generation lncRNA microarray
Project description:Heart failure (HF) is a leading cause of mortality and is associated with cardiac remodeling. Vulnerability to atrial fibrillation (AF) has been shown to be greater in the early stages of HF, whereas ventricular tachycardia/fibrillation develop during late stages. Here, we explore changes in gene expression that underlie the differential development of fibrosis and structural alterations that predispose to atrial and ventricular arrhythmias.
Project description:Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B We further identified associations between AF and rare structural variants due to deletions in CTNNA3 and duplications of GATA4 We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank Finally, we found that CRISPR-knockout of KDM5B in stem cell derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction Our results highlight the contribution of rare coding and structural variants to AF, the genetic link between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia