Objective: This study replicated a previous report that there may be substantial synergism between urbanicity (a proxy environmental risk factor) and familial clustering of psychotic disorder (a proxy genetic risk factor).
Method: The amount of synergism was estimated from the additive statistical interaction between urbanicity of place of birth and family history of schizophrenia or family history of any severe mental disorder in a population-based Danish cohort of 1,020,063 individuals.
Results: There was significant interaction between urbanicity and family history; between 20% and 35% of individuals who had been exposed to both of these risk factors had schizophrenia possibly because of their synergistic effects.
Conclusions: The results suggest that a substantial proportion of the population morbidity force of schizophrenia may be the result of gene-environment interactions associated with urbanicity.