Dissecting indirect genetic effects from peers in laboratory mice

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• dc.contributor.author Baud, Amelie
• dc.contributor.author Casale, Francesco Paolo
• dc.contributor.author Barkley-Levenson, Amanda M.
• dc.contributor.author Farhadi, Nilgoun
• dc.contributor.author Montillot, Charlotte
• dc.contributor.author Yalcin, Binnaz
• dc.contributor.author Nicod, Jerome
• dc.contributor.author Palmer, Abraham A.
• dc.contributor.author Stegle, Oliver
• dc.date.accessioned 2022-05-16T10:33:51Z
• dc.date.available 2022-05-16T10:33:51Z
• dc.date.issued 2021
• dc.description.abstract Background: The phenotype of an individual can be affected not only by the individual's own genotypes, known as direct genetic effects (DGE), but also by genotypes of interacting partners, indirect genetic effects (IGE). IGE have been detected using polygenic models in multiple species, including laboratory mice and humans. However, the underlying mechanisms remain largely unknown. Genome-wide association studies of IGE (igeGWAS) can point to IGE genes, but have not yet been applied to non-familial IGE arising from "peers" and affecting biomedical phenotypes. In addition, the extent to which igeGWAS will identify loci not identified by dgeGWAS remains an open question. Finally, findings from igeGWAS have not been confirmed by experimental manipulation. Results: We leverage a dataset of 170 behavioral, physiological, and morphological phenotypes measured in 1812 genetically heterogeneous laboratory mice to study IGE arising between same-sex, adult, unrelated mice housed in the same cage. We develop and apply methods for igeGWAS in this context and identify 24 significant IGE loci for 17 phenotypes (FDR < 10%). We observe no overlap between IGE loci and DGE loci for the same phenotype, which is consistent with the moderate genetic correlations between DGE and IGE for the same phenotype estimated using polygenic models. Finally, we fine-map seven significant IGE loci to individual genes and find supportive evidence in an experiment with a knockout model that Epha4 gives rise to IGE on stress-coping strategy and wound healing. Conclusions: Our results demonstrate the potential for igeGWAS to identify IGE genes and shed light into the mechanisms of peer influence.
• dc.description.sponsorship Funding: AB was supported by a fellowship from the Wellcome Trust (105941/Z/14/Z). This work was partially supported by a pilot grant from NIH (P50DA037844 to AAP). Research in the Stegle lab is supported by core funding from EMBL, the BMBF, the Volkswagen Foundation, and the EU (ERC project DECODE 810296)
• dc.format.mimetype application/pdf
• dc.identifier.citation Baud A, Casale FP, Barkley-Levenson A, Farhadi N, Montillot C, Yalcin B et al. Dissecting indirect genetic effects from peers in laboratory mice. Genome Biol. 2021 Jul 26;22(1):216. DOI: 10.1186/s13059-021-02415-x
• dc.identifier.doi http://dx.doi.org/10.1186/s13059-021-02415-x
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/53089
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/810296
• dc.rights © Amelie Baud et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genètica
• dc.subject.other Genòmica
• dc.subject.other Genotip
• dc.subject.other Fenotip
• dc.title Dissecting indirect genetic effects from peers in laboratory mice
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion