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PMID: 20231323 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Review

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 ·2010-05-00 ·Pages 509-27

Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE

Abstract

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.

MeSH Terms
Animals Brain/pathology,physiopathology Depressive Disorder/genetics Environment Genetic Predisposition to Disease/genetics Genome-Wide Association Study/methods Genotype Humans Models, Psychological Mood Disorders/genetics Primates/genetics,psychology Serotonin Plasma Membrane Transport Proteins/genetics,physiology Stress, Psychological/complications,genetics
Chemicals
Serotonin Plasma Membrane Transport Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Caspi Avshalom
Department of Psychology, and Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA. [email protected]
Hariri Ahmad R
Holmes Andrew
Uher Rudolf
Moffitt Terrie E
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Article Info
Journal
The American journal of psychiatry
Abbr.
Am J Psychiatry
ISSN
1535-7228
DOI
10.1176/appi.ajp.2010.09101452
Email
[email protected]
Published
2010-05-00
Epub
2010-00-15
Pages
509-27
Language
English
Region
United States
NLM ID
0370512
PMCID
PMC2943341
Subset
IM
Grants
Intramural NIH HHS · ZIA AA000411-06 · United States
NIA NIH HHS · AG032282 · United States
Medical Research Council · G9806489 · United Kingdom
NIMH NIH HHS · MH077874 · United States
Medical Research Council · G0100527 · United Kingdom
NIMH NIH HHS · R01 MH077874 · United States
NIMH NIH HHS · MH072837 · United States
NIMH NIH HHS · K01 MH072837 · United States
NICHD NIH HHS · HD061298 · United States
Medical Research Council · G0601483 · United Kingdom
NICHD NIH HHS · R01 HD061298 · United States
NIA NIH HHS · R01 AG032282 · United States
External Links
PubMed source DOI: 10.1176/appi.ajp.2010.09101452 PMC Full Text View journal details
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