Dissecting indirect genetic effects from peers in laboratory mice

Area of Science:

• Genetics
• Behavioral Science
• Animal Models

Background:

• Phenotypes are shaped by direct genetic effects (DGE) and indirect genetic effects (IGE) from interacting partners.
• IGE mechanisms are poorly understood, and genome-wide association studies of IGE (igeGWAS) have not been applied to non-familial peer interactions or experimentally validated.

Purpose of the Study:

• To develop and apply igeGWAS methods to non-familial peer interactions in mice.
• To identify IGE loci and genes influencing biomedical phenotypes.
• To investigate the overlap between IGE and DGE loci.

Main Methods:

• Utilized a dataset of 170 phenotypes from 1812 genetically heterogeneous mice housed in peer groups.
• Developed and applied igeGWAS methods to identify significant IGE loci.
• Fine-mapped IGE loci and validated findings using a knockout mouse model for Epha4.

Main Results:

• Identified 24 significant IGE loci for 17 phenotypes (FDR < 10%).
• Observed no overlap between IGE and DGE loci for the same phenotypes.
• Confirmed Epha4 as a gene mediating IGE on stress-coping and wound healing in a knockout model.

Conclusions:

• Demonstrated the utility of igeGWAS for discovering IGE genes.
• Provided insights into the genetic mechanisms underlying peer influence on phenotypes.