Evidence suggests that certain lifestyle factors moderate the manifestation of genetic susceptibility to complex diseases such as dementia and its co-morbidities. In these conditions multiple genetic loci explain greater variance in risk than a single candidate gene alone. The present study uses a large UK sample to investigate lifestyle and psychosocial factors that may interact with associations between polygenic scores for specific diseases (e.g. obesity, coronary artery disease, type 2 diabetes), and their manifestation in adulthood, with particular attention to sex-specific effects.