biostudies-literatureCaspi AEconomic and Social Research CouncilIntramural NIH HHSNICHD NIH HHSNIA NIH HHSMedical Research CouncilNIMH NIH HHS509-27https://www.ebi.ac.uk/biostudies/studies/S-EPMC2943341biostudies-literatureUnknown167(5)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),The American journal of psychiatryGenetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.PMC2943341MH077874R01 MH077874G0100527ES/H034897/1R01 AG032282G9806489G9817803BK01 MH072837MH072837ZIA AA000411-06HD061298R01 HD061298AG032282G0601483Hariri ARMoffitt TEHolmes AUher RCaspi AfalseGenetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits.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),2010-01-01T00:00:00Z2010 May2025-06-01T12:41:50.07Z2025-06-01T12:41:50.07ZS-EPMC29433412023132310.1176/appi.ajp.2010.09101452