Dataset Information

Annotation of susceptibility SNPs associated with atrial fibrillation.

ABSTRACT: OBJECTIVE:Genome-wide association studies (GWAS) and the candidate gene based association studies have identified a panel of variants associated with atrial fibrillation (AF), however, most of the identified single nucleotide polymorphisms (SNPs) were found located within intergenic or intronic genomic regions, and whether the positive SNPs have a real biological function is unknown, and the real disease causing gene need to be studied. RESULTS:The current results of the genetic studies including common variants identified by GWAS (338 index SNPs) and candidate gene based association studies (40 SNPs) were summarized. CONCLUSION:Our study suggests the relationship between genetic variants and possible targeted genes, and provides insight into potential genetic pathways underlying AF incidence and development. The results may provide an encyclopedia of AF susceptibility SNPs and shed light on the functional mechanisms of AF variants identified through genetic studies. METHODS:We summarized AF susceptibility SNPs identified by GWAS and candidate gene based association studies, and give a comprehensive functional annotation of all these AF susceptibility loci. by genomic annotation, microRNA binding prediction, promoter activity analysis, enhancer activity analysis, transcription factors binding activity prediction, expression quantitative trait loci (eQTL) analysis, long-range transcriptional regulatory function analysis, gene ontology and pathway enrichment analysis.

SUBMITTER: Xu C

PROVIDER: S-EPMC7521544 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Annotation of susceptibility SNPs associated with atrial fibrillation.

Xu Chengqi C Zhang Rongfeng R Xia Yunlong Y Xiong Liang L Yang Wei W Wang Pengyun P

Aging 20200909 17

<h4>Objective</h4>Genome-wide association studies (GWAS) and the candidate gene based association studies have identified a panel of variants associated with atrial fibrillation (AF), however, most of the identified single nucleotide polymorphisms (SNPs) were found located within intergenic or intronic genomic regions, and whether the positive SNPs have a real biological function is unknown, and the real disease causing gene need to be studied.<h4>Results</h4>The current results of the genetic s ...[more]

PMID: 32902410

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Project description:BACKGROUND:Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF. METHODS:Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation. RESULTS:Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13). CONCLUSIONS:Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Project description:Atrial fibrillation (AF) has heterogeneous patterns of presentation concerning symptoms, duration of episodes, AF burden, and the tendency to progress towards the terminal step of permanent AF. AF is associated with a risk of stroke/thromboembolism traditionally considered dependent on patient-level risk factors rather than AF type, AF burden, or other characterizations. However, the time spent in AF appears related to an incremental risk of stroke, as suggested by the higher risk of stroke in patients with clinical AF vs. subclinical episodes and in patients with non-paroxysmal AF vs. paroxysmal AF. In patients with device-detected atrial tachyarrhythmias, AF burden is a dynamic process with potential transitions from a lower to a higher maximum daily arrhythmia burden, thus justifying monitoring its temporal evolution. In clinical terms, the appearance of the first episode of AF, the characterization of the arrhythmia in a specific AF type, the progression of AF, and the response to rhythm control therapies, as well as the clinical outcomes, are all conditioned by underlying heart disease, risk factors, and comorbidities. Improved understanding is needed on how to monitor and modulate the effect of factors that condition AF susceptibility and modulate AF-associated outcomes. The increasing use of wearables and apps in practice and clinical research may be useful to predict and quantify AF burden and assess AF susceptibility at the individual patient level. This may help us reveal why AF stops and starts again, or why AF episodes, or burden, cluster. Additionally, whether the distribution of burden is associated with variations in the propensity to thrombosis or other clinical adverse events. Combining the improved methods for data analysis, clinical and translational science could be the basis for the early identification of the subset of patients at risk of progressing to a longer duration/higher burden of AF and the associated adverse outcomes.

Dataset Information

Annotation of susceptibility SNPs associated with atrial fibrillation.

Publications

Annotation of susceptibility SNPs associated with atrial fibrillation.

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