Genetic Variants Close to
 TTN
 ,
 NKX2-5
 , and
 MYH6
 Associate With AVNRT

Andreasen, Laura; Ahlberg, Gustav; Aegisdottir, Hildur M; Sveinbjörnsson, Garðar; Lundegaard, Pia R.; Hartmann, Jacob Peter; Paludan-Müller, Christian; Hadji-Turdeghal, Katra; Ghouse, Jonas; Pehrson, Steen; Jensen, Henrik Kjærulf; Riahi, Sam; Hansen, John‐Erik Stig; Sandgaard, Niels C. F.; Sørensen, Erik; Banasik, Karina; Sækmose, Susanne Gjørup; Bruun, Mie Topholm; Hjalgrim, Henrik; Erikstrup, Christian; Pedersen, Ole Birger; Wittig, Michael; Haunsø, Stig; Ostrowski, Sisse Rye; Consortium, Dbds Genomic; Franke, André; Brunak, Søren; Kanters, Jørgen K.; Ellervik, Christina; Bundgaard, Henning; Ullum, Henrik; Guðbjartsson, Daníel F.; Þorsteinsdóttir, Unnur; Hólm, Hilma; Arnar, Davíð O.; Stefánsson, Kāri; Svendsen, Jesper Hastrup; Olesen, Morten S.

doi:10.1161/circresaha.122.321556

Cited by 3 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed an association for AVNRT with a variant located intronic to TTN , which was in linkage disequilibrium with a variant reported in a prior AVNRT GWAS. 6…”

Section: Discussionmentioning

confidence: 99%

“…Our results support and extend previous findings suggesting an inherited basis for AVNRT and AVAP/ AVRT. [4][5][6] Limited reports have described rare monogenic forms of AVAP/AVRT, commonly in association with cardiomyopathy, 5,7 and familial aggregation of AVNRT has been observed. 4 More recently, a GWAS of roughly 2000 AVNRT cases from Denmark and Iceland identified 3 loci for AVNRT, 6 including the TTN and NKX2-5 loci that we identified in our current study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias

Weng,

Khurshid,

Hall

et al. 2024

Circ: Genomic and Precision Medicine

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT). METHODS: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies. RESULTS: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicates NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicates SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals. CONCLUSIONS: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.

show abstract

“…We also observed an association for AVNRT with a variant located intronic to TTN , which was in linkage disequilibrium with a variant reported in a prior AVNRT GWAS. 6…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias

Weng,

Khurshid,

Hall

et al. 2024

Circ: Genomic and Precision Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cao Y's study in 2016 suggested that a variation in the single nucleotide site of NKX2-5 may be linked to the occurrence of Atrial Septal Defect (ASD) (Cao et al, 2016). NKX2-5 regulates the proliferation, migration, differentiation, and function of cardiomyocytes through signaling pathways involving GATA4, MYH6, and others (Välimäki et al, 2017;Wang et al, 2020;Andreasen et al, 2022). Furthermore, several studies have suggested that NOTCH-1 mutation genes are among the most prevalent causes of Congenital Heart Disease (CHD) (Samira et al, 2020;Sarah et al, 2022) (Finsterer and Stöllberger, 2020).…”

Section: Functional Enrichment Analysis Of Mutant Genes In Pfo Patientsmentioning

confidence: 99%

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders

Li,

Xie,

Dai

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

BackgroundPatent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events.MethodsWe analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines.ResultsIn ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics.ConclusionWe identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5’s interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO’s genetic basis, suggesting potential therapeutic targets for future research.

show abstract

“… 5 Recently, a genome‐wide association study on AVNRT identified genetic associations close to genes, which have been associated with increased susceptibility to HF and dilated cardiomyopathy. 2 The findings suggest that AVNRT might be included in the concept of atrial cardiomyopathy and that it could be the first presentation of subsequent development of cardiomyopathy and HF among some patients.…”

mentioning

confidence: 95%

“…It affects younger individuals, has a female predominance, and is currently considered benign. 1 A recent genetic study on AVNRT has identified cardiomyocyte‐associated genes with the arrhythmia, 2 suggesting that there could be a clinically relevant association between AVNRT and more malignant cardiac phenotypes. Therefore, the study aimed to investigate the rates of cardiomyopathy, heart failure (HF), and death among patients with AVNRT treated with catheter ablation procedures in Denmark.…”

mentioning

confidence: 99%

Presence of Atrioventricular Nodal Reentrant Tachycardia Is Associated With Cardiomyopathy, Heart Failure, and Death

Paludan‐Müller,

Stampe,

Monfort

et al. 2024

JAHA

Self Cite

View full text Add to dashboard Cite

Genetic Variants Close to TTN , NKX2-5 , and MYH6 Associate With AVNRT

Cited by 3 publications

References 5 publications

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders

Presence of Atrioventricular Nodal Reentrant Tachycardia Is Associated With Cardiomyopathy, Heart Failure, and Death

Contact Info

Product

Resources

About