Evidence map›Paper›PMID 41672067›Full record

ArticleCell genomics2026

Discovery and characterization of gene-by-environment and epistatic genetic effects in a vertebrate model.

Bettina Welz, Saul Pierotti, Tomas Fitzgerald, Thomas Thumberger, Risa Suzuki, Philip Watson, Jana Fuss, Tiago Cordeiro da Trindade, Fanny Defranoux, Marcio Ferreira and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Bettina WelzCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg University, 69120 Heidelberg, Germany.
Saul PierottiEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK.
Tomas FitzgeraldEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK.
Thomas ThumbergerCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
Risa SuzukiCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg University, 69120 Heidelberg, Germany.
Philip WatsonCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg University, 69120 Heidelberg, Germany.
Jana FussCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg University, 69120 Heidelberg, Germany.
Tiago Cordeiro da TrindadeCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.
Fanny DefranouxEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK.
Marcio FerreiraEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK.
Kiyoshi NaruseNational Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8585, Aichi, Japan.
Felix LoosliInstitute of Biological and Chemical Systems, Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany. Electronic address: felix.loosli@kit.edu.
Jakob GiertenCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; Department of Pediatric Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany. Electronic address: jakob.gierten@cos.uni-heidelberg.de.
Joachim WittbrodtCentre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany. Electronic address: jochen.wittbrodt@cos.uni-heidelberg.de.
Ewan BirneyEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge CB10 1SD, UK. Electronic address: birney@ebi.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phenotypic variation arises from interactions between genetic and environmental factors, but disentangling these effects for complex traits remains challenging in observational cohorts like human biobanks. Model organisms with controlled genetic and environmental variation complement human studies in analyzing higher-order effects such as gene-by-environment (G×E) interactions, dominance, and epistasis. We utilized 76 medaka strains from the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel to compare heart rate plasticity across temperatures. An F2 segregation analysis identified 16 quantitative trait loci (QTLs), many exhibiting dominance, G×E, G×G, and G×G×E interactions. We experimentally validated four candidate genes, revealing temperature-sensitive heart rate effects. Finally, we simulated how genome-wide association study (GWAS) discovery power depends on statistical model choice. Our results suggest that the limited detection of non-additive effects in human GWASs stems from current study designs and sample sizes. This work demonstrates the value of controlled model organism studies for dissecting complex trait genetics and informing association study design.

Indexed as

Epistasis, GeneticGene-Environment InteractionOryziasAnimalsFemaleGenome-Wide Association StudyHumansModels, GeneticPhenotypePolymorphism, Single NucleotideQuantitative Trait Lociassociation studydominanceenvironmentepistasisG×EgeneticsG×GGWASmedakamodel organismQTL mapping

Identifiers

PMID41672067
PMCPMC13174225

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.