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Gene–environment interactions in common mental disorders: an update and strategy for a genome-wide search

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Abstract

A decade of research has demonstrated the explanatory potential of interplay between genetic variants and environmental factors in the development of common mental disorders. Initial findings have undergone tests of replicability and specificity. Some gene–environment interactions have been confirmed, some have not replicated and yet other turned out to be more specific than initially thought. Specific and complementary roles of genetic factors have been delineated: a common functional length polymorphism in the serotonin transporter gene (5-HTTLPR) moderated the effect of childhood maltreatment on chronic depression in adulthood, but did not substantially influence the effects of adult stressful life events on the onset of new depressive episodes; in contrast, a common functional polymorphism in the brain-derived neurotrophic factor gene (BDNF) moderated the effect of stressful life events in adulthood in triggering new depressive episodes, but did not influence the effects of childhood maltreatment. Molecular mechanisms underlying gene–environment interactions are being uncovered, including DNA methylation and other epigenetic modifications. New gene–environment interactions continue to be reported, still largely from hypothesis-driven research. Statistical and biological prioritization strategies are proposed to facilitate a systematic discovery of novel gene–environment interactions in genome-wide analyses.

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Notes

  1. This induced relationship is distinct from a gene–environment correlation (rGE) which denotes a true association between a genotype and exposure in the population (see reference [3]).

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Acknowledgments

Dr. Uher is supported by the Canada Research Chairs program (http://www.chairs-chaires.gc.ca/), the Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation and the European Commission Innovative Medicine Initiative Joint Undertaking (#115008).

Conflict of interest

Dr. Uher has received no personal income from pharmaceutical or biotech industry and holds no equity in companies active in medicine, pharmaceuticals or biotechnology. Dr. Uher consults for the World Health Organization. Dr Uher has collaborated with a number of pharmaceutical companies as part of the European Union Innovative Medicine Initiative funded NEWMEDS project.

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  1. Department of Psychiatry, Dalhousie University, 5909 Veterans’ Memorial Lane, Halifax, B3H 2E2, NS, Canada

    Rudolf Uher

  2. Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, UK

    Rudolf Uher

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Uher, R. Gene–environment interactions in common mental disorders: an update and strategy for a genome-wide search. Soc Psychiatry Psychiatr Epidemiol 49, 3–14 (2014). https://doi.org/10.1007/s00127-013-0801-0

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