Objectives In humans (and primates more generally), evolutionary fitness arises by two separate routes: conventional reproduction build around dyadic relationships and, reflecting the processes of group augmentation selection, how well individuals are embedded in their community. These processes are facilitated by a suite of genetically inherited neuroendocrines and neurotransmitters. It is not, however, known whether these effects are directly due to genetic factors or are mediated by aspects of personality, or whether there are sex differences in the way this is organised. Methods We examine whether dispositional factors related to the processing of social information, such as personality (Big 5 and Impulsivity), attachment style (Anxious and Avoidant dimensions) and sociocognitive capacity (emotion recognition) mediate associations between variation in receptor genes for oxytocin, vasopressin, beta-endorphin, dopamine, serotonin, testosterone and two core social relationship indices (the Sociosexual Orientation Index [SOI] and Support Network size). Results In men, variation in dopamine genes indirectly influences SOI through its effect on Impulsivity. In contrast, in women, variation in endorphin and vasopressin genes independently affect Openness to Experience, which mediates indirect effects of these genes on SOI. Moreover, endorphin gene variation also impacts on Network Size in women (but not men), via Extraversion. Conclusions These findings reveal that dispositional aspects of personality mediate some genetic effects on behaviour, thereby extending our understanding of how genetic and dispositional variation interact to determine individual differences in human sexual and social cognition and behaviour. The differences between the sexes seem to reflect differences in the two sexes' social strategies.