ArticleJournal of the American College of Cardiology2012
Chromosome 4q25 variants are genetic modifiers of rare ion channel mutations associated with familial atrial fibrillation.
Article in Journal of the American College of Cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 93 citations in OpenAlex.
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- The Yield of Genetic Testing and Putative Genetic Factors of Disease Heterogeneity in Long QT Syndrome Patients.International journal of molecular sciences · 2024Article
- Case report: Mutation inFrontiers in cardiovascular medicine · 2023Article
- Human induced pluripotent stem cell-derived atrial cardiomyocytes carrying an SCN5A mutation identify nitric oxide signaling as a mediator of atrial fibrillation.Stem cell reports · 2021Article
- The molecular genetic basis of atrial fibrillation.Human genetics · 2020Review
- Genetics and Epigenetics of Atrial Fibrillation.International journal of molecular sciences · 2020Review
- Atrial Fibrillation Is a Complex Trait: Very Complex.Circulation research · 2020Article
- How Will Genetics Inform the Clinical Care of Atrial Fibrillation?Circulation research · 2020Review
- PITX2 upregulation increases the risk of chronic atrial fibrillation in a dose-dependent manner by modulatingAnnals of translational medicine · 2020Article
- A comprehensive in silico analysis, distribution and frequency of humanJournal of cardiovascular and thoracic research · 2019Article
- Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells.Scientific reports · 2018Article
- Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups.JAMA network open · 2018Article
- A hERG mutation E1039X produced a synergistic lesion on IScientific reports · 2018Article
- Genetic Risk Scores for Atrial Fibrillation: Do They Improve Risk Estimation?The Canadian journal of cardiology · 2017Article
- EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: Definition, characterization, and clinical implication.Heart rhythm · 2017Review
- Genetic basis of atrial fibrillation.Genes & diseases · 2016Review
- Atrial Fibrillation Genetics: Is There a Practical Clinical Value Now or in the Future?The Canadian journal of cardiology · 2016Review
- EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2016Article
- EHRA/HRS/APHRS/SOLAECE expert consensus on Atrial cardiomyopathies: Definition, characterisation, and clinical implication.Journal of arrhythmia · 2016Article
- PITX2: a master regulator of cardiac channelopathy in atrial fibrillation?Cardiovascular research · 2016Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe aim of this study was to test the hypothesis that 2 common polymorphisms in the chromosome 4q25 region that have been associated with atrial fibrillation (AF) contribute to the variable penetrance of familial AF.
backgroundAlthough mutations in ion channels, gap junction proteins, and signaling molecules have been described for Mendelian forms of AF, penetrance is highly variable. Recent studies have consistently identified 2 common single-nucleotide polymorphisms in the chromosome 4q25 region as independent AF susceptibility alleles.
methodsEleven families in which AF was present in ≥2 members who also shared a candidate gene mutation were studied. These mutations were identified in all subjects with familial lone AF (n = 33) as well as apparently unaffected family members (age >50 years with no AF; n = 17).
resultsMutations were identified in SCN5A (n = 6), NPPA (n = 2), KCNQ1 (n = 1), KCNA5 (n = 1), and NKX2.5 (n = 1). In genetic association analyses, unstratified and stratified according to age of onset of AF and unaffected age >50 years, there was a highly statistically significant association between the presence of both common (rs2200733 and rs10033464) and rare variants and AF (unstratified p = 1 × 10(-8), stratified [age of onset <50 years and unaffected age >50 years] p = 7.6 × 10(-5)) (unstratified p < 0.0001, stratified [age of onset <50 years and unaffected age >50 years] p < 0.0001). Genetic association analyses showed that the presence of common 4q25 risk alleles predicted whether carriers of rare mutations developed AF (p = 2.2 × 10(-4)).
conclusionsCommon AF-associated 4q25 polymorphisms modify the clinical expression of latent cardiac ion channel and signaling molecule gene mutations associated with familial AF. These findings support the idea that the genetic architecture of AF is complex and includes both rare and common genetic variants.
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