ABSTRACT
Introduction Rates of psychiatric disorder vary across regions and demographic groups, suggesting widespread environmental influences (Dean & Murray, 2005). However, reported “environmental” effects are misleading as in reality they represent the effect of the environmental exposure and all the genetic influences that render an individual more sensitive to it. Genetic control of sensitivity to the environment is known as gene-environment interaction (G×E; Kendler & Eaves, 1986; Khoury, Beaty, & Cohen, 1993; Moffitt, Caspi, & Rutter, 2005). As study populations always contain a mix of genetically susceptible and non-susceptible individuals, associations between environmental exposures and psychiatric outcomes will be shifted towards the null if there is underlying G×E. For example, in a recent article by Clarke and colleagues, no association was detected between prenatal exposure to infection and schizophrenia. However, stratification of the population into those with and without evidence of genetic susceptibility revealed that prenatal exposure was associated with a large effect size only in the group with evidence of genetic susceptibility, suggestive of gene-environment interaction (Clarke, Tanskanen, Huttunen, Whittaker, & Cannon, 2009).
