Evidence map›Paper›PMID 29237690›Full record

ArticleCirculation. Cardiovascular genetics2017

Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease.

Christian Paludan-Müller, Gustav Ahlberg, Jonas Ghouse, Jesper H Svendsen, Stig Haunsø, Morten S Olesen

Open access · diamondAbstract read
PubMed Publisher
In one paragraph

Article in Circulation. Cardiovascular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 28% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Christian Paludan-MüllerFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.).
Gustav AhlbergFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.).
Jonas GhouseFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.).
Jesper H SvendsenFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.).
Stig HaunsøFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.).
Morten S OlesenFrom the Laboratory for Molecular Cardiology, Institute for Biomedical Sciences, University of Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Laboratory for Molecular Cardiology, Department of Cardiology, Heart Centre at Rigshospitalet, Copenhagen University Hospital, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark (C.P.-M., G.A., J.G., J.H.S., S.H., M.S.O.); and Department of Clinical Medicine, University of Copenhagen, Denmark (J.H.S., S.H.). morten.salling.olesen@gmail.com.
Danish National Research Foundation · DKUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDe novo variants in the exome occur at a rate of 1 per individual per generation, and because of the low reproductive fitness for de novo variants causing severe disease, the likelihood of finding these as standing variations in the general population is low. Therefore, this study sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database. METHODS AND

resultsWe performed a literature search for previous publications on de novo variants associated with severe arrhythmias and structural heart diseases and investigated whether these variants were present in the Exome Aggregation Consortium (ExAC) database (n=60 706). We identified monogenic variants in single case reports and smaller studies (≤200 subjects) and variants considered to increase susceptibility of disease in 3 larger trio studies (>1000 subjects). Of the monogenic variants, 11% (23/211) were present in ExAC, whereas 26% (802/3050) variants believed to increase susceptibility of disease were identified in ExAC. Monogenic de novo variants in ExAC had a total allele count of 109 and with ≈844 expected cases in ExAC, these variants would account for 13% of all cases in the studied diseases if truly monogenetic.

conclusionsWe observed numerous de novo variants associated with cardiac disease as standing variation in ExAC, thus these variants are less likely monogenetic causes or major risk contributors for cardiac disease. This highlights the importance of investigating the pathogenicity of de novo variants because they are not as exclusive and pathogenically evident as presumed previously.

Indexed as

Genetic VariationArrhythmias, CardiacDatabases, GeneticExomeFemaleGene FrequencyGenetic Predisposition to DiseaseHeart DiseasesHumansMaleMutation Ratearrhythmias, cardiacgenetic variationheart diseasesmutationrisk

Identifiers

PMID29237690
OpenAlexW2772046751

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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.