Genomic basis of atrial fibrillation

Bapat, Aneesh; Anderson, Chris; Ellinor, Patrick T.; Lubitz, Steven A.

doi:10.1136/heartjnl-2016-311027

Cited by 35 publications

(35 citation statements)

References 49 publications

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“…Interestingly, all of the causative genes of early repolarization syndrome have also been associated with atrial fibrillation. 24,25 There may be a common genetic background for atrial fibrillation and ventricular fibrillation related to early repolarization.…”

Section: Discussionmentioning

confidence: 99%

Early repolarization and risk of lone atrial fibrillation

Hasegawa

Watanabe

Ikami

et al. 2019

Cardiovasc electrophysiol

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Introduction Early repolarization syndrome is a recently proposed condition characterized by an early repolarization pattern in the electrocardiogram (ECG) and ventricular fibrillation in the absence of structural heart abnormalities. Although some studies have suggested that early repolarization is associated with frequency of atrial fibrillation, the association of early repolarization with atrial fibrillation is not well known. Hypothesis Early repolarization indicates the substrate for atrial fibrillation in addition to that for ventricular fibrillation. Method This study included 79 patients (57 men [72%]; age, 45 ± 12 years) aged less than 60 years who had paroxysmal lone atrial fibrillation and 395 age‐ and sex‐matched healthy controls (patient:control ratio, 1:5). Patients who had structural heart disease, hypertension, diabetes, hyperthyroidism, history of successful resuscitation, or the Brugada type ECG were excluded. ECGs recorded during sinus rhythm were compared between patients with atrial fibrillation and healthy controls. Results Early repolarization in the inferior and/or lateral leads was more common in patients with atrial fibrillation (25%) than controls (10%; P = 0.001). The location and magnitude of early repolarization were similar between the two groups. Other electrocardiographic measurements were not different between the two groups. Among patients with atrial fibrillation, there was no difference in clinical characteristics including age at atrial fibrillation development, sex, and body mass index between patients with early repolarization and those without early repolarization. Electrocardiographic measurements were not different between patients with early repolarization and those without early repolarization. Conclusion Early repolarization was associated with lone atrial fibrillation. Early repolarization may indicate increased susceptibility to atrial fibrillation.

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Section: Discussionmentioning

confidence: 99%

Early repolarization and risk of lone atrial fibrillation

Hasegawa

Watanabe

Ikami

et al. 2019

Cardiovasc electrophysiol

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“…VTE and AF are both blood-related polygenic conditions and are not fully understood genetically (Bapat, Anderson, Ellinor, & Lubitz, 2018; Hotoleanu, 2017). They share genetic risk factors and patho-physiological bases for clot formation (Shariff et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Identifying mutation‐driven changes in gene functionality that lead to venous thromboembolism

Wang

Bromberg

2019

Human Mutation

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Venous thromboembolism (VTE) is a common hematological disorder. VTE affects millions of people around the world each year and can be fatal. Earlier studies have revealed the possible VTE genetic risk factors in Europeans. The 2018 Critical Assessment of Genome Interpretation (CAGI) challenge had asked participants to distinguish between 66 VTE and 37 non-VTE African American (AA) individuals based on their exome sequencing data. We used variants from AA VTE association studies and VTE genes from DisGeNET database to evaluate VTE risk via four different approaches; two of these methods were most successful at the task. Our best performing method represented each exome as a vector of predicted functional effect scores of variants within the known genes. These exome vectors were then clustered with k-means. This approach achieved 70.8% precision and 69.7% recall in identifying VTE patients. Our second-best ranked method had collapsed the variant effect scores into gene-level function changes, using the same vector clustering approach for patient/control identification. These results show predictability of VTE risk in AA population and highlight the importance of variant-driven gene functional changes in judging disease status. Of course, more in-depth understanding of AA VTE pathogenicity is still needed for more precise predictions.

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“…The deletion/insertion of a 287-bp intronic DNA segment resulting in double-deletion or insertion/deletion genotypes of the angiotensin-converting enzyme gene has been associated with failure of antiarrhythmic drug therapy in AF (Darbar et al, 2007). GWAS studies have identified more than 30 genetic loci in association with AF, suggesting previously unrecognized potential mechanisms of the disease (Bapat et al, 2018). For example, a recent GWAS study identified a novel AF locus comprising intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle (Nielsen et al, 2018).…”

Section: Genetics Of Atrial Fibrillationmentioning

confidence: 99%

Mechanisms and Drug Development in Atrial Fibrillation

2018

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Atrial fibrillation is a highly prevalent cardiac arrhythmia and the most important cause of embolic stroke. Although genetic studies have identified an increasing assembly of AF-related genes, the impact of these genetic discoveries is yet to be realized. In addition, despite more than a century of research and speculation, the molecular and cellular mechanisms underlying AF have not been established, and therapy for AF, particularly persistent AF, remains suboptimal. Current antiarrhythmic drugs are associated with a significant rate of adverse events, particularly proarrhythmia, which may explain why many highly symptomatic AF patients are not receiving any rhythm control therapy. This review focuses on recent advances in AF research, including its epidemiology, genetics, and pathophysiological mechanisms. We then discuss the status of antiarrhythmic drug therapy for AF today, reviewing molecular mechanisms, and the possible clinical use of some of the new atrial-selective antifibrillatory agents, as well as drugs that target atrial remodeling, inflammation and fibrosis, which are being tested as upstream therapies to prevent AF perpetuation. Altogether, the objective is to highlight the magnitude and endemic dimension of AF, which requires a significant effort to develop new and effective antiarrhythmic drugs, but also improve AF prevention and treatment of risk factors that are associated with AF complications.

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Genomic basis of atrial fibrillation

Cited by 35 publications

References 49 publications

Early repolarization and risk of lone atrial fibrillation

Early repolarization and risk of lone atrial fibrillation

Identifying mutation‐driven changes in gene functionality that lead to venous thromboembolism

Mechanisms and Drug Development in Atrial Fibrillation

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