Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies
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Published version
Author(s)
Type
Journal Article
Abstract
Discrete categorization of Mendelian disease genes into dominant and recessive models often oversimplifies their underlying genetic architecture. Cardiomyopathies (CMs) are genetic diseases with complex etiologies for which an increasing number of recessive associations have recently been proposed. Here, we comprehensively analyze all published evidence pertaining to biallelic variation associated with CM phenotypes to identify high-confidence recessive genes and explore the spectrum of monoallelic and biallelic variant effects in established recessive and dominant disease genes. We classify 18 genes with robust recessive association with CMs, largely characterized by dilated phenotypes, early disease onset and severe outcomes. Several of these genes have monoallelic association with disease outcomes and cardiac traits in the UK Biobank, including LMOD2 and ALPK3 with dilated and hypertrophic CM, respectively. Our data provide insights into the complex spectrum of dominance and recessiveness in genetic heart disease and demonstrate how such approaches enable the discovery of unexplored genetic associations.
Date Issued
2023-11
Date Acceptance
2023-09-07
Citation
Nature Cardiovascular Research, 2023, 2 (11), pp.1078-1094
ISSN
2731-0590
Publisher
Springer Nature
Start Page
1078
End Page
1094
Journal / Book Title
Nature Cardiovascular Research
Volume
2
Issue
11
Copyright Statement
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.nature.com/articles/s44161-023-00346-3
Subjects
ABLATION
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
DEFICIENCY
DILATED CARDIOMYOPATHY
DISEASE
GENOTYPE
HYPERTROPHIC CARDIOMYOPATHY
INSIGHTS
LANDSCAPE
Life Sciences & Biomedicine
MUTATION LEADS
Science & Technology
VARIANTS
Publication Status
Published
Date Publish Online
2023-10-09