Leveraging genetic variation in the social partners to investigate effects of the social environment on behaviour (360G-Wellcome-105941_Z_14_Z)

I will use laboratory rodents to investigate indirect genetic effects (IGE) of social interactions between cage-mates in the weeks following weaning, a period corresponding to adolescence and early adulthood in humans[21]. My first goal is to characterise the genetic architecture of IGE, namely their contribution to phenotypic variation in the population - which I will compare to that of direct genetic effects (DGE), the number of quantitative trait loci (QTL) underlying IGE and their individu al effect-sizes. To do this, I will analyse three existing datasets comprising hundreds of measures of biomedical relevance and genome-wide genotypes for thousands of mice and rats[22-24]. In these analyses, I will model IGE and DGE jointly in the framework of mixed models[1]. My second goal is to establish whether modelling IGE and DGE jointly improves estimates of DGE and leads to better statistical power to map genetic loci underlying DGE. My third goal is to identify genes, molecular pathw ays, and phenotypes underlying behavioural IGE. I will use a combination of genetic mapping and expression profiling in a controlled experiment designed to maximise power to detect and dissect IGE. In this experiment, the genetic background of all focal mice will be the same and that of cage-mates heterogeneous.