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Citation
Tags
HERO ID
2855372
Reference Type
Journal Article
Subtype
Review
Title
Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits
Author(s)
Caspi, A; Hariri, AR; Holmes, A; Uher, R; Moffitt, TE
Year
2010
Is Peer Reviewed?
Yes
Journal
American Journal of Psychiatry
ISSN:
0002-953X
EISSN:
1535-7228
Volume
167
Issue
5
Page Numbers
509-527
Language
English
PMID
20231323
DOI
10.1176/appi.ajp.2010.09101452
Web of Science Id
WOS:000277237100009
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.
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