Evidence map›Paper›PMID 30071989›Full record

ArticleJournal of the American College of Cardiology2018

Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection.

Marjolijn Renard, Catherine Francis, Rajarshi Ghosh, Alan F Scott, P Dane Witmer, Lesley C Adès, Gregor U Andelfinger, Pauline Arnaud, Catherine Boileau, Bert L Callewaert and 12 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04751058 (Genetic Profile in Patients With Aortic Syndrome), which is not on this map. Cited by 150 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 7 pooled it
17.5field-weighted citation impact, top 1% 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.

NCT04751058 completednot on this mapstarted 2021, after this paper: background citation

Genetic Profile in Patients With Aortic Syndrome

TypeobservationalSponsorHospitales Universitarios Virgen del RocíoRan2021 to 2022Enrolled73ConditionsGene Abnormality, Acute Aortic SyndromeArmsgenetic analysis
3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 7 syntheses or guidelines pooled it, 291 citations in OpenAlex.

  1. X-linked genetic associations in sporadic thoracic aortic dissection.American journal of medical genetics. Part A · 2024
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  18. Journal of vascular surgery cases and innovative techniques · 2026
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90 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 14 institutions in 7 countries.

Marjolijn RenardCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Catherine FrancisNational Heart and Lung institute, Imperial College London, London, United Kingdom; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom.
Rajarshi GhoshDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Alan F ScottMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland.
P Dane WitmerMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland.
Lesley C AdèsChildren's Hospital at Westmead, Sydney, New South Wales, Australia.
Gregor U AndelfingerCardiovascular Genetics, Department of Pediatrics, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
Pauline ArnaudDépartement de Génétique et Centre de Référence Maladies Rares Syndrome de Marfan et pathologies apparentées, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; LVTS, INSERM U1148, Université Paris Diderot, Hôpital Bichat, Paris, France.
Catherine BoileauDépartement de Génétique et Centre de Référence Maladies Rares Syndrome de Marfan et pathologies apparentées, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; LVTS, INSERM U1148, Université Paris Diderot, Hôpital Bichat, Paris, France.
Bert L CallewaertCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Dongchuan GuoDepartment of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas.
Nadine HannaDépartement de Génétique et Centre de Référence Maladies Rares Syndrome de Marfan et pathologies apparentées, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; LVTS, INSERM U1148, Université Paris Diderot, Hôpital Bichat, Paris, France.
Mark E LindsayThoracic Aortic Center and Cardiovascular Genetics Program, Departments of Medicine and Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
Hiroko MorisakiDepartment of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan; Tokyo University of Technology School of Health Sciences, Tokyo, Japan.
Takayuki MorisakiDepartment of Medical Genetics, Sakakibara Heart Institute, Tokyo, Japan; Tokyo University of Technology School of Health Sciences, Tokyo, Japan.
Nicholas PachterGenetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Leema RobertDepartment of Clinical Genetics, Guys and St. Thomas' Hospital, London, United Kingdom.
Lut Van LaerCenter of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Harry C DietzHoward Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bart L LoeysCenter of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Dianna M MilewiczDepartment of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas.
Julie De BackerCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Department of Cardiology, Ghent University Hospital, Ghent, Belgium. Electronic address: Julie.Debacker@ugent.be.
Ghent University Hospital · BEHôpital Necker-Enfants Malades · FRJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USTokyo University of Technology · JPUniversity of Antwerp · BEBaylor College of Medicine · USCentre Hospitalier Universitaire Sainte-Justine · CAChildren's Hospital at Westmead · AUHoward Hughes Medical Institute · USKing Edward Memorial Hospital · AUMassachusetts General Hospital · USRoyal Brompton Hospital · GBSt Thomas' Hospital · GB

Funding

Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
The Clinical Genome Resource - Expert Curation and EHR IntegrationU41HG009650 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BERG, JONATHAN S · 2017 to 2020
$13.3M
A Knowledge Base for Clinically Relevant Genes and VariantsU01HG007437 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BERG, JONATHAN S, EVANS, JAMES PHILIP · 2013 to 2016
$9.0M
MUSCLE METABOLISM AND CIRCULATORY CONTROL IN EXERCISEK04HL001581 · NHLBI · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI LEWIS, STEVEN F · 1986 to 1990
–
British Heart Foundation FS/15/81/31817NCATS NIH HHS UL1 TR000371NHGRI NIH HHS U01 HG007437NHGRI NIH HHS U41 HG009650
6 · The paper itself

Abstract

backgroundThoracic aortic aneurysms progressively enlarge and predispose to acute aortic dissections. Up to 25% of individuals with thoracic aortic disease harbor an underlying Mendelian pathogenic variant. An evidence-based strategy for selection of genes to test in hereditary thoracic aortic aneurysm and dissection (HTAAD) helps inform family screening and intervention to prevent life-threatening thoracic aortic events.

objectivesThe purpose of this study was to accurately identify genes that predispose to HTAAD using the Clinical Genome Resource (ClinGen) framework.

methodsWe applied the semiquantitative ClinGen framework to assess presumed gene-disease relationships between 53 candidate genes and HTAAD. Genes were classified as causative for HTAAD if they were associated with isolated thoracic aortic disease and were clinically actionable, triggering routine aortic surveillance, intervention, and family cascade screening. All gene-disease assertions were evaluated by a pre-defined curator-expert pair and subsequently discussed with an expert panel.

resultsGenes were classified based on the strength of association with HTAAD into 5 categories: definitive (n = 9), strong (n = 2), moderate (n = 4), limited (n = 15), and no reported evidence (n = 23). They were further categorized by severity of associated aortic disease and risk of progression. Eleven genes in the definitive and strong groups were designated as "HTAAD genes" (category A). Eight genes were classified as unlikely to be progressive (category B) and 4 as low risk (category C). The remaining genes were recent genes with an uncertain classification or genes with no evidence of association with HTAAD.

conclusionsThe ClinGen framework is useful to semiquantitatively assess the strength of gene-disease relationships for HTAAD. Gene categories resulting from the curation may inform clinical laboratories in the development, interpretation, and subsequent clinical implications of genetic testing for patients with aortic disease.

Indexed as

Aortic Aneurysm, ThoracicAortic DissectionFemaleGenetic Predisposition to DiseaseGenetic TestingHumansMaleReproducibility of ResultsClinGengene curationgene-disease relationshipthoracic aortic aneurysmthoracic aortic dissection

Identifiers

PMID30071989
PMCPMC6378369
OpenAlexW2887657552

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Registered trials

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.