Phenome-wide genetic framework to identify mechanisms of social effects

Abstract Phenotypes are shaped not only by an individual’s genotype (direct genetic effects, DGE) and environment but also by the genetic composition of social partners through indirect genetic effects (IGE). Although IGE have been detected across many traits and species, their mechanisms remain largely unknown, particularly for physiological traits. Here we introduce a phenome-wide genetic framework that identifies proxy phenotypes for the heritable traits of social partners mediating IGE by estimating genetic correlations between IGE on focal phenotypes and DGE on measured traits. Applying this approach to two large, outbred mouse datasets comprising hundreds of behavioural and physiological phenotypes, we find that behavioural traits are neither more affected by IGE nor better proxies for the traits mediating them, challenging the prevailing behavioural-centric view of social effects. Instead, immune, metabolic and growth phenotypes are both affected by IGE and informative proxies for their underlying mechanisms, potentially reflecting the social transmission of gut microbes. Our framework provides a novel strategy to better understand the genetic basis of complex traits and uncover mechanisms of social effects.