PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Wolf, E. J.,2014 PMID: 24677629
Citation	Wolf, E. J., et al. (2014). "A genome-wide association study of clinical symptoms of dissociation in a trauma-exposed sample." Depress Anxiety 31(4): 352-360.
Phenotype	Dissociative symptom severity
Trauma	Combat (military veterans)
Study Design	Case-control
Study Type	Genome-wide association study
Sample Size	484 samples
SNP/Marker Size	1,197,702 SNPs
Predominant Ethnicity	Caucasian
Population	White, non-Hispanic
Gender	314 male and 170 female
Age	Mean age=52 years, range:21-75.

Detail Info

Sample Diagnosis	DSM-IV
Related Diagnostic Tools	All interviews were administered by clinicians with either an MA or PhD in psychology. The Clinician Administered PTSD Scale (CAPS). Traumatic Life Events Questionnaire.
Sample Status	484 had scores on the CAPS interview items assessing derealization and depersonalization and were included in these analyses. In this final sample, 60.5% of the sample met criteria for a lifetime diagnosis of PTSD (247 veterans and 45 nonveteran partners). All interviews were digitally recorded for the purposes of evaluating diagnostic reliability (see below) and maintaining quality control. The principal investigator of the study (MWM) oversaw weekly meetings of interviewers to review videotapes, discuss diagnostic concerns, and prevent rater drift. Veterans and their nonveteran partners took part in identical but separate assessment procedures. Partners included in the study had trauma exposure were not necessarily "controls."
Controls Exposed	No
Replication Size	None
Result Summary	RESULTS: Ten SNPs evidenced suggestive association with dissociation (P-value < E-05). No SNPs met genome-wide significance criteria (P-value < 5E-08). The peak SNP was rs263232 (beta=1.4, P-value= 6.12E-07), located in the adenylyl cyclase 8 (ADCY8) gene; a second SNP in the suggestive range was rs71534169 (beta=1.63, P-value=3.79E-06), located in the dipeptidyl-peptidase 6 (DPP6) gene. CONCLUSIONS: ADCY8 is integral for long-term potentiation and synaptic plasticity and is implicated in fear-related learning and memory and long-term memory consolidation. DPP6 is critical for synaptic integration and excitation. These genes may exert effects on basic sensory integration and cognitive processes that underlie dissociative phenomena.
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 15)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs263232	Dissociative symptom severity	ADCY8	Linear regression: B=1.43, SE=0.28, P-value=6.12E-07, R²=0.05. Controlling for PTSD severity: P-value=5.66E-07, modified by sex: P-value=0.09.	The SNP with the strongest association with dissociation. Th...... The SNP with the strongest association with dissociation. The effect of the SNP remained suggestive after controlling for PTSD severity and was not significantly modified by sex. More...	Trend
rs2466273	Dissociative symptom severity	KIAA1456	Linear regression: B=1.31, SE=0.29, P-value=7.10E-06, R²=0.04. Sex and SNP effects were found for rs2466273: B(interaction) =-1.63, P-value= .007; B(men)=0.74, P-value=.04; B(women)=2.36, P-value=3E-06.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. And it showed suggestive evidence of an association with sex, such that the effects were greater in women compared to men. More...	Trend
rs263238	Dissociative symptom severity	ADCY8	P-value<0.05	Follow-up evaluation of ADCY8 revealed four other SNPs (rs43...... Follow-up evaluation of ADCY8 revealed four other SNPs (rs4339660, rs7015079, rs263238, and rs263234) that were nominally associated with dissociation severity (smallest P-value= .01). More...	Non-significant
rs263234	Dissociative symptom severity	ADCY8	P-value<0.05	Follow-up evaluation of ADCY8 revealed four other SNPs (rs43...... Follow-up evaluation of ADCY8 revealed four other SNPs (rs4339660, rs7015079, rs263238, and rs263234) that were nominally associated with dissociation severity (smallest P-value= .01). More...	Non-significant
rs62488971	Dissociative symptom severity	KIAA1456	Linear regression: B=1.58, SE=0.35, P-value=8.37E-06, R²=0.04. Sex and SNP effects were found for rs62488971: B(interaction) =-2.44, P-value= .0008; B(men)=0.70, P-value=.11; B(women)=3.14, P-value=2E-07.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. And it showed suggestive evidence of an association with sex, such that the effects were greater in women compared to men. More...	Trend
rs4339660	Dissociative symptom severity	ADCY8	P-value<0.05	Follow-up evaluation of ADCY8 revealed four other SNPs (rs43...... Follow-up evaluation of ADCY8 revealed four other SNPs (rs4339660, rs7015079, rs263238, and rs263234) that were nominally associated with dissociation severity (smallest P-value= .01). More...	Non-significant
rs7015079	Dissociative symptom severity	ADCY8	P-value<0.05	Follow-up evaluation of ADCY8 revealed four other SNPs (rs43...... Follow-up evaluation of ADCY8 revealed four other SNPs (rs4339660, rs7015079, rs263238, and rs263234) that were nominally associated with dissociation severity (smallest P-value= .01). More...	Non-significant
rs682457	Dissociative symptom severity	MIR3166	Linear regression: B=1.11, SE=0.22, P-value=1.09E-06, R²=0.05. After covarying for PTSD severity (with PTSD severity in the model), P-value=6.99E-07.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. More...	Trend
rs77006546	Dissociative symptom severity	Intergenic (Near CMAHP)	Linear regression: B=0.70, SE=0.38, P-value=9.60E-06, R²=0.04. After covarying for PTSD severity (with PTSD severity in the model), P-value= .0002.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. More...	Trend
rs71534169	Dissociative symptom severity	DPP6	Linear regression: B=1.63, SE=0.35, P-value=3.79E-06, R²=0.04. Controlling for PTSD severity: P-value=3.96E-05. SNP and sex interaction: B=-2.34, P-value=0.002. Stratifying by sex, among women: B=3.26, P-value=6.96E?07, among men: B=0.93, P-value=.03.	A second SNP in the suggestive range was rs71534169. The eff...... A second SNP in the suggestive range was rs71534169. The effect of the SNP remained significant after controlling for PTSD severity, and there was a significant SNP and sex interaction. Stratifying by sex showed the effect to be stronger among women than men. More...	Trend
rs9306235	Dissociative symptom severity	COMT	Association with dissociation: P-value= .04, gene-wide permutation testing: P-value= .42.	It showed a nominally significant association that did not w...... It showed a nominally significant association that did not withstand gene-wide permutation testing. More...	Non-significant
rs77963519	Dissociative symptom severity	Intergenic (Closest gene is MEX3B)	Linear regression: B=1.56, SE=0.33, P-value=3.71E-06, R²=0.04.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. More...	Trend
rs9725031	Dissociative symptom severity	Intergenic (Closest gene is SIPA1L2)	Linear regression: B=1.13, SE=0.25, P-value=7.72E-06, R²=0.04. Sex and SNP effects were found for rs9725031: B(interaction) =-1.48, P-value= .004; B(men)=0.57, P-value=.07; B(women)=2.05, P-value=1.17E-06.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. And it showed suggestive evidence of an association with sex, such that the effects were greater in women compared to men. More...	Trend
rs1915919	Dissociative symptom severity	KAT2B	Linear regression: B=0.74, SE=0.16, P-value=7.99E-06, R²=0.04.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. More...	Trend
rs2460905	Dissociative symptom severity	KIAA1456	Linear regression: B=1.38, SE=0.30, P-value=4.95E-06, R²=0.04. Sex and SNP effects were found for rs2460905: B(interaction) =-1.72, P-value= .005; B(men)=0.75, P-value=.05; B(women)=2.46, P-value=1.44E-06.	It showed suggestive evidence of association with dissociati...... It showed suggestive evidence of association with dissociation. In follow-up analyses, the association between this SNP and dissociation severity remained significant after covarying for PTSD severity. And it showed suggestive evidence of an association with sex, such that the effects were greater in women compared to men. More...	Trend