Evidence map›Paper›PMID 40307248›Full record

ArticleNature communications2025

Natural genetic variation quantitatively regulates heart rate and dimension.

Jakob Gierten, Bettina Welz, Tomas Fitzgerald, Thomas Thumberger, Rashi Agarwal, Oliver Hummel, Adrien Leger, Philipp Weber, Kiyoshi Naruse, David Hassel and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jakob Gierten *Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8143-1918
Bettina Welz *Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.
Tomas Fitzgerald *European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.ORCID http://orcid.org/0000-0002-2370-8496
Thomas ThumbergerCentre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8485-457X
Rashi AgarwalCentre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0504-899X
Oliver HummelCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Adrien LegerEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.ORCID http://orcid.org/0000-0001-8772-6776
Philipp WeberDepartment of Cardiology, Heidelberg University Hospital, Heidelberg, Germany.
Kiyoshi NaruseNational Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.ORCID http://orcid.org/0000-0001-9185-3495
David HasselGerman Centre for Cardiovascular Research (DZHK); Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Norbert HübnerCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID http://orcid.org/0000-0002-1218-6223
Ewan BirneyEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK. birney@ebi.ac.uk.ORCID http://orcid.org/0000-0001-8314-8497
Joachim WittbrodtCentre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany. jochen.wittbrodt@cos.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-8550-7377

Funding

The medaka Kiyosu panel: dissecting GxE effects of environmental chemicalsR01ES029917 · NIEHS · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI BIRNEY, EWAN, GOLDSTONE, JARED VERRILL · 2019 to 2023
$2.1M
Deutsche Herzstiftung (German Heart Foundation) S/02/17Deutsches Zentrum für Herz-Kreislaufforschung (Deutsches Zentrum für Herz-Kreislaufforschung e.V.) 81X2500189EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) Synergy grant 810172/IndiGeneJoachim Herz Stiftung (Joachim Herz Foundation) Add-On Fellowship for Interdisciplinary ScienceNIEHS NIH HHS R01 ES029917
6 · The paper itself

Abstract

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.

Indexed as

Genetic VariationHeartHeart RateOryziasAnimalsChromosome MappingFemaleGene EditingHeart VentriclesMalePhenotypeQuantitative Trait Loci

Identifiers

PMID40307248
PMCPMC12044080

What OpenQuestion holds

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Registered trials

None linked

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.