Table Info

Table 2.

The advantages and disadvantages of using zebrafish for validation of GWAS loci from DILI studies

Advantages	Disadvantages
Ease of application of drugs dissolved in the embryonic media in embryos and early larvae Ease of liver imaging in intact organism	Differences in the liver architecture between zebrafish and humans may alter pathogenesis of DILI species-specifically
Ability to screen a high number of biological replicates using a wide range of doses	Most GWAS loci are non-coding and may not be well conserved between species
Availability of various mutant strains of GWAS loci as ready-to-use models Speedy generation of knockout and transgenic strains	Difficulty in functional assessment of knock-out and knock-in strains because of the presence of paralogous copies of genes in zebrafish (one-to-many genes)
Presence of many GWAS human loci with orthologs in the zebrafish genome	Not all human GWAS loci have orthologs in zebrafish
Observed similarity between humans and zebrafish in their pathogenic response to drugs	Varying levels of sequence similarity between protein coding genes of zebrafish and humans
Potential for generating specialized zebrafish cohorts for eQTL studies	Requirement of a large collection of strains/individuals for idiosyncratic DILI studies in zebrafish

Declarations

Acknowledgments

Authors thank Emine Gelinci and Ebru Önal for recording zebrafish images.

Author contributions

GCA: Conceptualization, Visualization, Writing—review & editing. AMA, MCC: Visualization, Writing—review & editing. KAA: Writing—review & editing. OK: Conceptualization, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Not applicable.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

GCA and OK are supported by The Scientific and Technological Research Council of Türkiye (TUBITAK). GCA: [119S698], [118C484], OK: [116Z388]. GCA and OK are supported by the European Union COST action [CA17112] PRO-EURO-DILI-NET and Horizon Europe [101095679] project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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