Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies.

Nature cardiovascular research
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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 and 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.

Year of Publication
2023
Journal
Nature cardiovascular research
Volume
2
Issue
11
Pages
1078-1094
Date Published
12/2023
ISSN
2731-0590
DOI
10.1038/s44161-023-00346-3
PubMed ID
38666070
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