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American Journal of Epidemiology Advance Access originally published online on February 19, 2009
American Journal of Epidemiology 2009 169(6):704-711; doi:10.1093/aje/kwn397
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American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Modification of the Association Between Serotonin Transporter Genotype and Risk of Posttraumatic Stress Disorder in Adults by County-Level Social Environment

Karestan C. Koenen, Allison E. Aiello, Erin Bakshis, Ananda B. Amstadter, Kenneth J. Ruggiero, Ron Acierno, Dean G. Kilpatrick, Joel Gelernter and Sandro Galea

Correspondence to Dr. Karestan C. Koenen, Department of Society, Human Development, and Health, Harvard School of Public Health, 677 Huntington Avenue, Kresge 613, Boston, MA 02115 (e-mail: kkoenen{at}hsph.harvard.edu).

Received for publication July 9, 2008. Accepted for publication November 25, 2008.

Although both genetic factors and features of the social environment are important predictors of posttraumatic stress disorder (PTSD), there are few data examining gene-social environment interactions in studies of PTSD. The authors examined whether features of the social environment (county-level crime rate and unemployment) modified the association between the serotonin protein gene (SLC6A4) promoter variant (5-HTTLPR) and risk of current PTSD in a sample of 590 participants from the 2004 Florida Hurricane Study. Interviews conducted in 2005 were used to obtain individual-level risk factor measures and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PTSD diagnoses. DNA was extracted from salivary samples. County-level crime and unemployment rates were assessed from Federal Bureau of Investigation and US Census data, respectively. There was a significant interaction between 5-HTTLPR genotype and both crime rate (odds ratio = 2.68, 95% confidence interval: 1.09, 6.57) and unemployment rate (odds ratio = 3.67, 95% confidence interval: 1.42, 9.50) in logistic regression models predicting PTSD risk, after adjustment for individual-level determinants of PTSD. Stratified analyses indicated that the "s" allele of the 5-HTTLPR polymorphism was associated with decreased risk of PTSD in low-risk environments (low crime/unemployment rates) but increased risk of PTSD in high-risk environments. These results suggest that social environment modifies the effect of 5-HTTLPR genotype on PTSD risk.

crime; genetics; serotonin; serotonin plasma membrane transport proteins; SLC6A4 protein, human; social environment; stress disorders, post-traumatic; unemployment

Abbreviations: CI, confidence interval; 5-HTTLPR, serotonin transporter polymorphism; OR, odds ratio; PTSD, posttraumatic stress disorder


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K. C. Koenen and S. Galea
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