CITATION.cff

cff-version: 1.2.0
title: >-
  Penetrance and disease expression of (likely)
  pathogenic variants associated with inherited
  cardiomyopathies in the general population
message: >-
  If you use this software, please cite it using the
  metadata from this file.
preffered-citation:
type: article 
authors:
  - given-names: Mimount
    name-particle: M
    family-names: Bourfiss
  - given-names: Marion
    name-particle: M
    family-names: van Vugt
    email: m.vanvugt-2@umcutrecht.nl
    affiliation: UMC Utrecht
    orcid: 'https://orcid.org/0000-0002-6634-1989'
  - given-names: Abdulrahman 
    name-particle: I
    family-names: Alasiri
  - given-names: Bram
    name-particle: B
    family-names: Ruijsink
  - given-names: Jessica
    name-particle: J
    family-names: van Setten
  - given-names: Amand
    name-particle: A F
    family-names: Schmidt
  - given-names: Dennis
    name-particle: D
    family-names: Dooijes
  - given-names: Esther
    name-particle: E
    family-names: Puyol-Anton
  - given-names: Birgitta
    name-particle: K
    family-names: Velthuis
  - given-names: Peter
    name-particle: J P
    family-names: van Tintelen
  - given-names: Anneline
    name-particle: S J M
    family-names: te Riele
  - given-names: Annette
    name-particle: F
    family-names: Baas
  - given-names: Folkert
    name-particle: W
    family-names: Asselbergs
identifiers:
  - type: doi
    value: 10.1101/2022.01.06.22268837
    description: MedrXiv
repository-code: >-
  https://github.com/CirculatoryHealth/Inherited-cardiomyopathies
abstract: >
  Background. Pathogenic and likely pathogenic
  variants associated with arrhythmogenic right
  ventricular cardiomyopathy (ARVC), dilated
  cardiomyopathy (DCM) and hypertrophic
  cardiomyopathy (HCM) are recommended to be reported
  as secondary findings in genome sequencing studies.
  This provides opportunities for early diagnosis,
  but also fuels uncertainty in variant carriers
  (G+), since disease penetrance is incomplete. We
  assessed the prevalence and disease expression of
  G+ in the general population.

  Methods. We identified pathogenic and likely
  pathogenic variants associated with ARVC, DCM
  and/or HCM in 200,643 UK Biobank individuals, who
  underwent whole exome sequencing. We calculated the
  prevalence of G+ and analysed the frequency of
  cardiomyopathy/heart failure diagnosis. In
  undiagnosed individuals, we analysed early signs of
  disease expression.

  Results. We found a prevalence of 1:578, 1:251 and
  1:149 for (likely) pathogenic variants associated
  with ARVC, DCM and HCM respectively. Compared to
  controls, cardiovascular mortality was higher in
  DCM G+ (OR 1.67 [95% CI 1.04;2.59], p=0.030), but
  similar in ARVC and HCM G+ (p≥0.100). More
  specifically, cardiomyopathy or heart failure
  diagnosis were more frequent in DCM G+ (OR 3.66
  [95% CI 2.24;5.81], p=4.9×10-7) and HCM G+ (OR 3.03
  [95% CI 1.98;4.56], p=5.8×10-7), but comparable in
  ARVC G+ (p=0.172). In contrast, ARVC G+ had more
  ventricular arrhythmias (p=3.3×10-4). In
  undiagnosed individuals, left ventricular ejection
  fraction was reduced in DCM G+ (p=0.009).

  Conclusions. In the general population, (likely)
  pathogenic variants associated with ARVC, DCM or
  HCM are not uncommon. Although G+ have increased
  mortality and morbidity, disease penetrance in
  these carriers from the general population remains
  low (1.2-3.1%). Follow-up decisions in case of
  incidental findings should not be based solely on
  the variant, but on multiple factors, including
  family history.
keywords:
  - whole exome sequencing
  - genetics
  - >-
    arrhythmogenic right ventricular cardiomyopathy,
    dilated cardiomyopathy
  - dilated cardiomyopathy
  - hypertrophic cardiomyopathy
license: CC-BY-4.0