Novel Perspectives on Genetic Evaluation in Early-Onset Atrial Fibrillation: Clinical Implications and Future Directions
Abstract
:1. Introduction
2. Materials and Methods
3. Clinical and Genetic Landscape of Early-Onset Atrial Fibrillation
4. Atrial Cardiomyopathy and Early Onset Atrial Fibrillation
5. Current Guideline Recommendation on Genetic Testing in Atrial Fibrillation
6. Clinical Implications of Genetic Testing
7. Challenges, Limitations, and Future Directions
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AF | Atrial Fibrillation |
AFL | Atrial Flutter |
AtCM | Atrial Cardiomyopathy |
GWAS | Genome-Wide Association Study |
eQTL | Expression Quantitative Trait Locus |
BrS | Brugada Syndrome |
EOAF | Early-Onset Atrial Fibrillation |
LOF | Loss of Function |
LQTS | Long QT Syndrome |
SQTS | Short QT Syndrome |
TTN | Titin |
CPVT | Catecholaminergic Polymorphic Ventricular Tachycardia |
P/LP | Pathogenic or Likely Pathogenic |
IKs | Slow Delayed Rectifier Potassium Current |
DCM | Dilated Cardiomyopathy |
OMIM | Online Mendelian Inheritance in Man |
HCM | Hypertrophic Cardiomyopathy |
ACM/ARVC | Arrhythmogenic Cardiomyopathy/Arrhythmogenic Right Ventricular Cardiomyopathy |
PRS | Polygenic Risk Score |
CPVT | Catecholaminergic Polymorphic Ventricular Tachycardia |
LQTS | Long QT Syndrome |
SCN | Sodium Channel Voltage-Gated |
AtCM | Atrial Cardiomyopathy |
ECG | Electrocardiogram |
MRI | Magnetic Resonance Imaging |
TTNtv | Titin-Truncating Variants |
PRS | Polygenic Risk Score |
NPPA | Natriuretic Peptide Precursor A |
ICD | Implantable Cardioverter-Defibrillator |
ACMG | American College of Medical Genetics |
VCL | Vinculin |
VUS | Variant of Uncertain Significance |
ACC/AHA | American College of Cardiology/American Heart Association |
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Ref. | Study Type | Main Findings |
---|---|---|
1 | Review | Comorbidities and lifestyle factors influence AF burden |
2 | Review | HTN, diabetes, alcohol, and sleep apnea increase AF risk |
3 | GBD analysis | AF burden increasing globally in older adults |
4 | GBD analysis | AF varies by national income levels |
5 | Genetic study | Genetic insights from 50,000 AF cases |
6 | Consensus | Genetic testing guidance for inherited cardiac diseases |
7 | GWAS | Multi-ethnic GWAS identified AF loci |
8 | Meta-GWAS/PRS | Polygenic risk prediction for AF improved |
9 | Prospective cohort | Younger age at AF diagnosis increases stroke risk |
10 | Consensus | Consensus on genetic testing for cardiac diseases |
11 | Book Chapter | Role of genetics in pediatric/adult cardiomyopathy |
12 | Review | Clinical implications of cardiomyopathy genetics |
13 | NGS Genetic study | DSM p.R127P variant linked to high cardiac mortality |
14 | Retrospective cohort | AF in cardiomyopathy predicts poor outcomes |
15 | Population study | Early-onset AF is a marker for cardiomyopathy |
16 | Genetic study | Monogenic variants in early-onset AF identified |
17 | Guideline | 2023 ACC/AHA AF management guideline |
18 | Review | Genetic architecture of AF |
19 | Case–control study | TTN LoF variants linked to early-onset AF |
20 | Cohort study | High TTN LoF prevalence in early-onset AF |
21 | Cohort study | TTNtv carriers with AF have high cardiomyopathy risk |
22 | Genetic study | Genetic bases of early-onset AF without risk factors |
23 | Cohort study | Rare variants in early-onset AF predict higher mortality |
24 | Population study | Titin and lifestyle interact in AF risk |
25 | Review | Genetic basis of atrial cardiomyopathy |
26 | Case series | NPPA mutation linked to atrial cardiomyopathy |
27 | Animal model | MYL4 dysfunction causes atrial abnormalities |
28 | Genetic study | MYL4 frameshift causes early-onset AF |
29 | Case series | SCN5A mutation leads to atrial standstill |
30 | Case report | LMNA mutation linked to atrial standstill |
31 | Genetic study | Atrial dysfunction precedes ventricular in LMNA mutation |
32 | Retrospective cohort | TTNtv linked to familial/early onset AF |
33 | Genetic study | Genetic predisposition + clinical risk factors affect AF risk |
34 | Genetic risk model | PRS for AF risk equivalent to monogenic mutations |
35 | Polygenic risk score | New insights into AF biology from Biobank data |
36 | Guideline | ESC 2024 management of AF guideline recommendations |
37 | Guideline | ACMG 2021 secondary findings guidance |
38 | Metanalysis | AF risk higher in athletes than general population |
39 | Review | Acute alcohol consumption triggers AF episodes |
40 | Review | Genetic testing in early-onset AF |
41 | Cohort study | Rare variant prevalence in patients with early-onset AF |
42 | Position statement | ESC guidance on cardiomyopathy variant interpretation |
43 | Case series | LMNA/LAMA4 mutations in familial ARVC |
44 | Cohort study | LMNA mutation raises thromboembolic risk |
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Laconi, A.; Fancello, T.; Solinas, G.; Casu, G. Novel Perspectives on Genetic Evaluation in Early-Onset Atrial Fibrillation: Clinical Implications and Future Directions. Cardiogenetics 2025, 15, 15. https://doi.org/10.3390/cardiogenetics15020015
Laconi A, Fancello T, Solinas G, Casu G. Novel Perspectives on Genetic Evaluation in Early-Onset Atrial Fibrillation: Clinical Implications and Future Directions. Cardiogenetics. 2025; 15(2):15. https://doi.org/10.3390/cardiogenetics15020015
Chicago/Turabian StyleLaconi, Angelo, Tatiana Fancello, Giuliana Solinas, and Gavino Casu. 2025. "Novel Perspectives on Genetic Evaluation in Early-Onset Atrial Fibrillation: Clinical Implications and Future Directions" Cardiogenetics 15, no. 2: 15. https://doi.org/10.3390/cardiogenetics15020015
APA StyleLaconi, A., Fancello, T., Solinas, G., & Casu, G. (2025). Novel Perspectives on Genetic Evaluation in Early-Onset Atrial Fibrillation: Clinical Implications and Future Directions. Cardiogenetics, 15(2), 15. https://doi.org/10.3390/cardiogenetics15020015