Evidence map›Paper›PMID 28549997›Full record

ArticleHeart rhythm2017

Deep sequencing of atrial fibrillation patients with mitral valve regurgitation shows no evidence of mosaicism but reveals novel rare germline variants.

Emilie Gregers, Gustav Ahlberg, Thea Christensen, Javad Jabbari, Kirstine O Larsen, Cecilie B Herfelt, Kristoffer M Henningsen, Laura Andreasen, Jens J Thiis, Jens Lund and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Heart rhythm, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Atrial fibrillation-a complex polygenetic disease.European journal of human genetics : EJHG · 2021
    Review
  11. Review
  12. Article
  13. Genetics of atrial fibrillation: an update.Current opinion in cardiology · 2018
    Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Emilie GregersDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gustav AhlbergDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Thea ChristensenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
Javad JabbariDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kirstine O LarsenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
Cecilie B HerfeltDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kristoffer M HenningsenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Laura AndreasenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens J ThiisDepartment of Cardiothoracic Surgery, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens LundDepartment of Cardiothoracic Surgery, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Susanne HolmeDepartment of Cardiothoracic Surgery, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Stig HaunsøDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bo H BentzenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
Nicole SchmittDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Science, University of Copenhagen, Copenhagen, Denmark.
Jesper H SvendsenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: jesper.hastrup.svendsen@regionh.dk.
Morten S OlesenDanish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark; Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
University of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia. Valvular heart disease is a strong predictor, yet the underlying molecular mechanisms are unknown.

objectiveThe purpose of this study was to investigate the prevalence of somatic variants in AF candidate genes in an AF patient population undergoing surgery for mitral valve regurgitation (MVR) to determine whether these patients are genetically predisposed to AF.

methodsDNA was extracted from blood and left atrial tissue from 44 AF patients with MVR. Using next-generation sequencing, we investigated 110 genes using the HaloPlex Target Enrichment System. MuTect software was used for identification of somatic point variants. We functionally characterized selected variants using electrophysiologic techniques.

resultsNo somatic variants were identified in the cardiac tissue. Thirty-three patients (75%) had a rare germline variation in ≥1 candidate genes. Fourteen variants were novel. Fifteen variants were predicted damaging or likely damaging in ≥6 in silico predictions. We identified rare variants in genes never directly associated with AF: KCNE4, SCN4B, NEURL1, and CAND2. Interestingly, 7 patients (16%) had variants in genes involved in cellular potassium handling. The variants KCNQ1 (p.G272S) and KCNH2 (p.A913V) resulted in gain of function due to faster activation (KCNQ1) and slowed deactivation kinetics (KCNQ1, KCNH2).

conclusionWe did not find any somatic variants in patients with AF and MVR. Surprisingly, we found that our cohort of non-lone AF patients might, like lone AF patients, be predisposed to AF by rare germline variants. Our findings emphasize the extent of still unknown factors in the pathogenesis of AF.

Indexed as

Genetic Predisposition to DiseaseMosaicismAgedAtrial FibrillationComputational BiologyDNADNA Mutational AnalysisFemaleFollow-Up StudiesGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansMaleMiddle AgedMitral Valve InsufficiencyRetrospective StudiesDNAAtrial fibrillationBioinformaticsCardiac tissueGeneticsMitral valve regurgitationSomatic mutationsSomatic variants

Identifiers

PMID28549997
OpenAlexW2619993401

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.