Natural genetic variation quantitatively regulates heart rate and dimension Article Swipe
Jakob Gierten
,
Bettina Welz
,
Tomas Fitzgerald
,
Thomas Thumberger
,
Rashi Agarwal
,
Oliver Hummel
,
Adrien Léger
,
Philipp Weber
,
Kiyoshi Naruse
,
David Hassel
,
Norbert Hübner
,
Ewan Birney
,
Joachim Wittbrodt
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-59425-7
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-59425-7
The polygenic contribution to heart development and function along the health-disease continuum remains unresolved. To gain insight into the genetic basis of quantitative cardiac phenotypes, we utilize highly inbred Japanese rice fish models, Oryzias latipes , and Oryzias sakaizumii . Employing automated quantification of embryonic heart rates as core metric, we profiled phenotype variability across five inbred strains. We observed maximal phenotypic contrast between individuals of the HO5 and the HdrR strain. HO5 showed elevated heart rates associated with embryonic ventricular hypoplasia and impaired adult cardiac function. This contrast served as the basis for genome-wide mapping. In an F2 segregation population of 1192 HO5 x HdrR embryos, we mapped 59 loci (173 genes) associated with heart rate. Experimental validation of the top 12 candidate genes by gene editing revealed their causal and distinct impact on heart rate, development, ventricle size, and arrhythmia. Our study uncovers new diagnostic and therapeutic targets for developmental and electrophysiological cardiac diseases and provides a novel scalable approach to investigate the intricate genetic architecture of the vertebrate heart.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41467-025-59425-7
- https://www.nature.com/articles/s41467-025-59425-7.pdf
- OA Status
- gold
- Cited By
- 2
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410013849
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410013849Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41467-025-59425-7Digital Object Identifier
- Title
-
Natural genetic variation quantitatively regulates heart rate and dimensionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-04-30Full publication date if available
- Authors
-
Jakob Gierten, Bettina Welz, Tomas Fitzgerald, Thomas Thumberger, Rashi Agarwal, Oliver Hummel, Adrien Léger, Philipp Weber, Kiyoshi Naruse, David Hassel, Norbert Hübner, Ewan Birney, Joachim WittbrodtList of authors in order
- Landing page
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https://doi.org/10.1038/s41467-025-59425-7Publisher landing page
- PDF URL
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https://www.nature.com/articles/s41467-025-59425-7.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.nature.com/articles/s41467-025-59425-7.pdfDirect OA link when available
- Concepts
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Variation (astronomy), Dimension (graph theory), Genetic variation, Natural (archaeology), Evolutionary biology, Biology, Genetics, Mathematics, Gene, Physics, Paleontology, Combinatorics, AstrophysicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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54Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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