Year: 2026
Type: preprint
Abstract: The phenotype of a focal individual can be affected not only by the individual’s own genes (direct genetic effects, DGE) but also by genes of other individuals it interacts with (indirect genetic effects, IGE). Better understanding IGE can help better understand the impact and mechanisms of social effects. Here, we investigated, in laboratory mice, the modulation of IGE by genetic background of the focal individual (“social epistasis”) and by sex. We focused on IGE arising from Epha4 , a gene that has been associated with the individual’s own stress-related and social behaviours (i.e. DGE) and the stress-coping behaviour and wound healing of the other mice in the cage (i.e. IGE). Among four different genetic backgrounds for focal mice, significant IGE from Epha4 were detected in CBA females only. A formal model selection analysis was consistent with the modulation of IGE by the similarity of the genetic backgrounds of the focal mouse and its Epha4 cage mate, as well as by sex. Observations of fighting in cages of males with dissimilar genetic backgrounds suggested aggression might underpin these modulatory effects, which prompted to us to expand the conceptual framework describing the mechanisms of social epistasis. Thus, our results strengthen the emerging view that IGE are not fixed properties of social genotypes but can depend on the genetic and sex context of interacting individuals, revealing an underexplored layer of their genetic architecture. Author summary The phenotype of a focal individual can be affected by genes of other individuals it interacts with (“indirect genetic effects”, IGE). The extent to which IGE depend on the context, in particular the genetic background and sex of the interacting individuals, is poorly understood. This study focused on IGE from Epha4 in male and female laboratory mice and measured stress-coping behaviour and ear wound healing in focal mice from four genetic backgrounds co-housed with a cage mate with or without a mutation in Epha4 . The effects of partner Epha4 genotype varied across genetic backgrounds and sexes. We expanded the conceptual framework describing how the context can modulate IGE. Our results have important implications for the design of IGE experiments.
Language: English
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7215813112