PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Xie, P.,2012 PMID: 22693124
Citation	Xie, P., et al. (2012). "Serotonin transporter 5-HTTLPR genotype moderates the effects of childhood adversity on posttraumatic stress disorder risk: a replication study." Am J Med Genet B Neuropsychiatr Genet 159B(6): 644-652.
Phenotype	Lifetime PTSD
Trauma	Various
Study Design	Case-control
Study Type	Candidate gene association study, Gene-environment interaction study
Sample Size	2779 European Americans and 2399 African Americans
SNP/Marker Size	1 Variant
Predominant Ethnicity	Caucasian, Black
Population	African American, European American
Gender	44.0% female
Age	Mean age=40.5 years, SD=11.2, ranging from 18 to 85 years.

Detail Info

Sample Diagnosis	SSADDA, DSM-IV
Related Diagnostic Tools	All subjects were interviewed by trained interviewers using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA), which yields DSM-IV diagnoses for a variety of psychiatric disorders, including PTSD (Pierucci-Lagha and others 2007; Pierucci-Lagha and others 2005).
Sample Status	None of the subjects were included in our previous study. The recruitment procedures were nearly identical to the prior study except that the previous sample was ascertained as small nuclear families, and the present sample is composed mostly of unrelated subjects, with only 4.4% of the subjects from small nuclear families. The interview also elicited diagnostic criteria for depression and substance use disorders. Major depressive disorder and substance dependence diagnoses were made based on DSM-IV criteria.
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	We used logistic regression analyses to explore the interaction effect of 5-HTTLPR genotype and childhood adversity on PTSD risk. We found that, as reported in our previous study, in individuals with childhood adversity, the presence of one or two copies of the S allele of 5-HTTLPR increased the risk to develop PTSD. This gene-environment interaction effect was present in European Americans (EAs), but not in African Americans (AAs) (EAs, OR=1.49, 95% CI=1.07-2.08, P-value=0.019; AAs, OR=0.90, 95% CI=0.60-1.35, P-value=0.62). The statistical power to detect this interaction effect was increased when data were combined with those from our previous study (Xie and others 2009). The findings reported here replicate those from our previous work, adding to a growing body of research demonstrating that the 5-HTTLPR genotype moderates risk for anxiety and depression phenotypes in the context of stress and adverse events.
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 1)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
5-HTTLPR	Lifetime PTSD	SLC6A4	genotype (After adjusting for age and sex), EA: OR=0.97, 95% CI=0.83-1.12, P-value=0.65; AA: OR=1.04, 95% CI=0.87-1.25, P-value=0.67.	After adjusting for age and sex, genotype was not significan...... After adjusting for age and sex, genotype was not significantly associated with PTSD. More...	Non-significant

Gene * Environment result reported by this study (count: 1)

Marker	Phenotype	Related Gene	Environment	Statistical Values	Author Comments	Marker's Category
5-HTTLPR	Lifetime PTSD	SLC6A4	Childhood adversity (participants were asked whether, by age 13, they had witnessed or experienced a violent crime, had been sexually abused, or had been physically abused)	5-HTTLPR genotype x childhood adversity interaction: EA, OR=1.49, 95% CI=1.07-2.08, P-value=0.019; AA, OR=0.90, 95% CI=0.60-1.35, P-value=0.62. In combined sample:EA, OR=1.52, 95% CI=1.12-2.06, P-value=0.0069; AA, OR=1.14, 95% CI=0.79-1.64, P-value=0.50.	5-HTTLPR genotype x childhood adversity interaction was sign...... 5-HTTLPR genotype x childhood adversity interaction was significantly associated with lifetime PTSD diagnosis in EAs, but not in AAs. The interaction effect was calculated again after adding the diagnosis of major depressive disorder into the logistic regression model as a covariate. Including depression in the model did not change the interaction effect on PTSD. We combined the data from the current study with those from our previous study investigating the interaction effect of 5-HTTLPR and childhood adversity on PTSD risk. With the increased sample size, the power to detect the interaction effect is increased, but the effect in AAs remained non-significant. After adjusting for the effects of substance dependence, the interaction of childhood adversity and 5-HTTLPR genotype on PTSD diagnosis remained largely unchanged. More...	Significant