PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Xie, P.,2010 PMID: 20393453
Citation	Xie, P., et al. (2010). "Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder." Neuropsychopharmacology 35(8): 1684-1692.
Phenotype	Lifetime PTSD
Trauma	Not mentioned.
Study Design	Case-control
Study Type	Candidate gene association study, Gene-environment interaction study
Sample Size	1143 European Americans and 1284 African Americans
SNP/Marker Size	4 SNPs
Predominant Ethnicity	Caucasian, Black
Population	African American, European American
Gender	54.4% male
Age	Mean age=38.6 years, SD=10.8.

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) (Pierucci-Lagha et al, 2007; Pierucci-Lagha et al, 2005).
Sample Status	Two thousand four hundred twenty-seven subjects were enrolled in this study. Blood samples were collected during linkage and association studies of the genetics of cocaine, opioid, and alcohol dependence. The SSADDA Environment section assesses childhood adversity, among other features. Participants were asked whether, by age 13, they had witnessed or experienced a violent crime, had been sexually abused, or had been physically abused. Endorsement of any of these adverse childhood experiences was coded as positive for exposure to childhood adversity.
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in?FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of?FKBP5?polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD.?FKBP5?genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, whereas they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also?FKBP5?polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene x environment effect of?FKBP5?and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations.
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 4)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs9470080	Lifetime PTSD	FKBP5	In African American, main effect: OR=0.58, 95%CI=0.41-0.82, P-value=0.0025. In European American, it showed no significant association between genotypes and PTSD (data not shown).	In the primary analyses, logistic GEE regression showed no s...... In the primary analyses, logistic GEE regression showed no significant association betweenFKBP5?genotypes and PTSD in AAs or EAs (data not shown). When main FKBP5 genotype effects and their interaction effects with childhood adversity were entered into the logistic regression models simultaneously, all four SNPs were significantly associated with the development of PTSD in AAs. After correction for multiple testing, it remained significant (Bonferroni correction, threshold P-value=0.05/4=0.0125). SNP rs9470080 had the strongest conditional effect. However, in EAs, none of the four SNPs were associated with the development of PTSD when the interactive effect of genotype and childhood adversity was also in the logistic regression model.The results from the secondary analyses are very similar to the primary results. More...	Significant
rs9296158	Lifetime PTSD	FKBP5	In African American, main effect: OR=0.61, 95%CI=0.43-0.88, P-value=0.0081. In European American, it showed no significant association between genotypes and PTSD (data not shown).	In the primary analyses, logistic GEE regression showed no s...... In the primary analyses, logistic GEE regression showed no significant association betweenFKBP5?genotypes and PTSD in AAs or EAs (data not shown). When main FKBP5 genotype effects and their interaction effects with childhood adversity were entered into the logistic regression models simultaneously, all four SNPs were significantly associated with the development of PTSD in AAs. After correction for multiple testing, it remained significant (Bonferroni correction, threshold P-value=0.05/4=0.0125). However, in EAs, none of the four SNPs were associated with the development of PTSD when the interactive effect of genotype and childhood adversity was also in the logistic regression model.The results from the secondary analyses are very similar to the primary results. More...	Significant
rs3800373	Lifetime PTSD	FKBP5	In African American, main effect: OR=0.62, 95%CI=0.43-0.89, P-value=0.0103. In European American, it showed no significant association between genotypes and PTSD (data not shown).	In the primary analyses, logistic GEE regression showed no s...... In the primary analyses, logistic GEE regression showed no significant association betweenFKBP5?genotypes and PTSD in AAs or EAs (data not shown). When main FKBP5 genotype effects and their interaction effects with childhood adversity were entered into the logistic regression models simultaneously, all four SNPs were significantly associated with the development of PTSD in AAs. After correction for multiple testing, it remained significant (Bonferroni correction, threshold P-value=0.05/4=0.0125). However, in EAs, none of the four SNPs were associated with the development of PTSD when the interactive effect of genotype and childhood adversity was also in the logistic regression model. The results from the secondary analyses are very similar to the primary results. More...	Significant
rs1360780	Lifetime PTSD	FKBP5	In African American, main effect: OR=0.63, 95%CI=0.44-0.91, P-value=0.0135. In European American, it showed no significant association between genotypes and PTSD (data not shown).	In the primary analyses, logistic GEE regression showed no s...... In the primary analyses, logistic GEE regression showed no significant association betweenFKBP5?genotypes and PTSD in AAs or EAs (data not shown). When main FKBP5 genotype effects and their interaction effects with childhood adversity were entered into the logistic regression models simultaneously, all four SNPs were significantly associated with the development of PTSD in AAs. After correction for multiple testing, it didn't remained significant (Bonferroni correction, threshold P-value=0.05/4=0.0125). However, in EAs, none of the four SNPs were associated with the development of PTSD when the interactive effect of genotype and childhood adversity was also in the logistic regression model.The results from the secondary analyses are very similar to the primary results. More...	Significant

Gene * Environment result reported by this study (count: 4)

Marker	Phenotype	Related Gene	Environment	Statistical Values	Author Comments	Marker's Category
rs9296158	Lifetime PTSD	FKBP5	Childhood adversity (Three types of childhood adversity were considered in this study: namely, witnessing or experiencing a violent crime, experiencing sexual abuse, and experiencing physical abuse.)	In African Americans, the effects of childhood adversity x FKBP5 genotype on risk for PTSD (before correction for multiple tests): OR=1.69, CI=1.05-2.71, P-value=0.0282.	Before correction for multiple tests, it significantly modif...... Before correction for multiple tests, it significantly modified the effect of childhood adversity on risk for PTSD in AAs (These same two SNPs also were the most significant in the previous study by Binder et al, (2008).) After Bonferroni correction, the signal didn't remain significant. There was no interactive effect of FKBP5 genotypes and childhood adversity in EAs. The results from the secondary analyses are very similar to the primary results. More...	Significant
rs9470080	Lifetime PTSD	FKBP5	Childhood adversity (Three types of childhood adversity were considered in this study: namely, witnessing or experiencing a violent crime, experiencing sexual abuse, and experiencing physical abuse.)	In African Americans, the effects of childhood adversity x FKBP5 genotype on risk for PTSD (before correction for multiple tests): OR=1.96, CI=1.24-3.10, P-value=0.0040.	Before correction for multiple tests, two of the four SNPs i...... Before correction for multiple tests, two of the four SNPs in FKBP5 significantly modified the effect of childhood adversity on risk for PTSD in AAs (rs9296158: OR=1.69, 95% CI=1.05-2.71, P=0.03; rs9470080: OR=1.96, 95% CI=1.24-3.10, P=0.004). (These same two SNPs also were the most significant in the previous study by Binder et al, (2008).) After Bonferroni correction, the signal from rs9470080 remained significant. There was no interactive effect of FKBP5 genotypes and childhood adversity in EAs. The results from the secondary analyses are very similar to the primary results. More...	Significant
rs3800373	Lifetime PTSD	FKBP5	Childhood adversity (Three types of childhood adversity were considered in this study: namely, witnessing or experiencing a violent crime, experiencing sexual abuse, and experiencing physical abuse.)	In African Americans, the effects of childhood adversity x FKBP5 genotype on risk for PTSD (before correction for multiple tests): OR=1.49, CI=0.93-2.39, P-value=0.0958.	There was no interactive effect of FKBP5 genotypes and child...... There was no interactive effect of FKBP5 genotypes and childhood adversity in EAs or AAs. The results from the secondary analyses are very similar to the primary results. More...	Non-significant
rs1360780	Lifetime PTSD	FKBP5	Childhood adversity (Three types of childhood adversity were considered in this study: namely, witnessing or experiencing a violent crime, experiencing sexual abuse, and experiencing physical abuse.)	In African Americans, the effects of childhood adversity x FKBP5 genotype on risk for PTSD (before correction for multiple tests): OR=1.58, CI=0.98-2.54, P-value=0.0602.	There was no interactive effect of FKBP5 genotypes and child...... There was no interactive effect of FKBP5 genotypes and childhood adversity in EAs or AAs. The results from the secondary analyses are very similar to the primary results. More...	Non-significant