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Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.

Publication ,  Journal Article
Caspi, A; Hariri, AR; Holmes, A; Uher, R; Moffitt, TE
Published in: The American journal of psychiatry
May 2010

Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (GxE) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sensitivity in nonhuman primates; and 4) studies of stress sensitivity and genetically engineered 5-HTT mutations in rodents. The authors then dispel some misconceptions and offer recommendations for GxE research. The authors discuss how GxE interaction hypotheses can be tested with large and small samples, how GxE research can be carried out before as well as after replicated gene discovery, the uses of GxE research as a tool for gene discovery, the importance of construct validation in evaluating GxE research, and the contribution of GxE research to the public understanding of genetic science.

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Published In

The American journal of psychiatry

DOI

EISSN

1535-7228

ISSN

0002-953X

Publication Date

May 2010

Volume

167

Issue

5

Start / End Page

509 / 527

Related Subject Headings

  • Stress, Psychological
  • Serotonin Plasma Membrane Transport Proteins
  • Psychiatry
  • Primates
  • Mood Disorders
  • Models, Psychological
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American Journal of Psychiatry, 167(5), 509–527. https://doi.org/10.1176/appi.ajp.2010.09101452
Caspi, Avshalom, Ahmad R. Hariri, Andrew Holmes, Rudolf Uher, and Terrie E. Moffitt. “Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.The American Journal of Psychiatry 167, no. 5 (May 2010): 509–27. https://doi.org/10.1176/appi.ajp.2010.09101452.
Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American journal of psychiatry. 2010 May;167(5):509–27.
Caspi, Avshalom, et al. “Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.The American Journal of Psychiatry, vol. 167, no. 5, May 2010, pp. 509–27. Epmc, doi:10.1176/appi.ajp.2010.09101452.
Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American journal of psychiatry. 2010 May;167(5):509–527.
Journal cover image

Published In

The American journal of psychiatry

DOI

EISSN

1535-7228

ISSN

0002-953X

Publication Date

May 2010

Volume

167

Issue

5

Start / End Page

509 / 527

Related Subject Headings

  • Stress, Psychological
  • Serotonin Plasma Membrane Transport Proteins
  • Psychiatry
  • Primates
  • Mood Disorders
  • Models, Psychological
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease