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Terrie E. Moffitt, PhD; Avshalom Caspi, PhD; Michael Rutter, MD, FRS

Arch Gen Psychiatry. 2005;62:473-481.

The purpose of this article is to promote research that tests hypotheses of measured gene-environment interaction (GxE). A GxE occurs when the effect of exposure to an environmental pathogen on health is conditional on a person’s genotype (or conversely, when environmental experience moderates genes’ effects on health). Gene-environment interactions were thought to be rare in psychiatry, but empirical findings of measured GxEs are now emerging. However, the current high level of curiosity about GxE is accompanied by uncertainty about the feasibility of GxE research and by pragmatic questions about how to carry out good GxE studies. First, we summarize emerging evidence about GxE in psychiatric disorders. Second, we describe 7 strategic steps that may be used to organize further hypothesis-driven studies of GxE. Third, we explain the potential benefits of the measured-GxE approach for basic neuroscience and for gene hunting. We suggest that in psychiatric genetics, ignoring nurture handicaps the field’s capacity to make new discoveries about nature.

Author Affiliations: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, England (Drs Moffitt, Caspi, and Rutter); and Department of Psychology, University of Wisconsin, Madison (Drs Moffitt and Caspi).

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