PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Chang, S. C.,2012 PMID: 21912390
Citation	Chang, S. C., et al. (2012). "No association between ADCYAP1R1 and post-traumatic stress disorder in two independent samples." Mol Psychiatry 17(3): 239-241.
Phenotype	PTSD, Total number of PTSD symptoms, PTSD symptom severity, PTSD symptom subscale scores, Current PTSD, Chronic PTSD
Trauma	Not mentioned.
Study Design	Case-control
Study Type	Candidate gene association study
Sample Size	Nurses' Health Study II (NHSII):2,528 women. The second sample: 6,074 individuals.
SNP/Marker Size	1 SNP
Predominant Ethnicity	Black, Caucasian
Population	European American, African American
Gender	Nurses' Health Study II (NHSII): all females. The second sample: 3353 participants AA (51.8% male) and 2721 participants were classified as EA (57.7% male).
Age	Nurses' Health Study II (NHSII): mean age=55 years, SD=4.4. The second sample: 3353 participants were classified as AA (mean age=41.1 years, SD=9.1) and 2721 participants were classified as EA (mean age=37.7 years, SD=11.0).

Detail Info

Sample Diagnosis	DSM-IV
Related Diagnostic Tools	Nurses' Health Study II (NHSII): We assessed lifetime trauma exposure and PTSD in 2690 women using a clinically validated structured diagnostic telephone interview. The second sample: All subjects were interviewed by trained interviewers using the Semi-Structured Assessment for Drug Dependence and Alcoholism.
Sample Status	The second sample contained 6074 individuals recruited for genetic studies of substance dependence at five US sites.
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	Ressler et al. recently examined the pituitary adenylate cyclase-activating peptide (PACAP) ligand/type 1 receptor (PAC1) pathway in post-traumatic stress disorder (PTSD) in a predominantly African American (AA) sample. Association analyses examining 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes further identified rs2267735, a SNP, in a putative estrogen response element (ERE) within the ADCYAP1R1 gene, which predicted PTSD diagnosis and symptoms in females. We sought to replicate the genetic association between rs2267735 and PTSD in two independent samples. In summary, we were unable to replicate the association between rs2267735 and PTSD in either AA or EA females in these two large independent samples. Our findings do not, however, exclude the possibility that the PACAP-PAC1 receptor pathway has a role in the production of PTSD. Our replication samples differ principally from Ressler's sample on three grounds: sample selection, demographic characteristics and participant's social context. Ressler's sample was recruited from patients in medical clinics, and comprised of relatively young (mean age=39.6 years), low-income, largely unemployed, AAs, highly trauma exposed, inner city residents. In contrast, the NHSII sample was population-based, older EAs with much higher income and education. The Yale samples comprised of both AA and EA young substance dependence cases and unaffected controls, related or unrelated, who participated in the study focused on the genetics of substance dependence (mean age=39 years).
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 6)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs2267735	PTSD symptom severity	ADCYAP1	Unadjusted P-value=0.48-0.98.	In contrast with the previous findings, rs2267735 was not as...... In contrast with the previous findings, rs2267735 was not associated with PTSD symptom severity. More...	Non-significant
rs2267735	PTSD symptom subscale scores	ADCYAP1	Unadjusted P-value=0.48-0.98.	In contrast with the previous findings, rs2267735 was not as...... In contrast with the previous findings, rs2267735 was not associated with PTSD symptom subscale scores. More...	Non-significant
rs2267735	Total number of PTSD symptoms	ADCYAP1	Unadjusted P-value=0.48-0.98.	In contrast with the previous findings, rs2267735 was not as...... In contrast with the previous findings, rs2267735 was not associated with total number of PTSD symptoms. More...	Non-significant
rs2267735	PTSD	ADCYAP1	NHSII: In the unadjusted model, 'CC' genotype carriers compared with 'CG/GG' carriers: OR=1.12, 95% CI=0.90-1.40, adjusted OR=1.18, 95%CI=0.94-1.49. In pre-menopausal women, 'CC' genotype in the pre-menopausal: aOR=1.29, 95%CI=0.96-1.74, n=1471 or natural menopause group: aOR=0.86, 95%CI=0.43-1.73, n=440. In second sample: under either additive or dominant genetic models with respect to the G allele: dominant model: AA female: OR=1.13, 95%CI=0.86-1.50; AA male: OR=0.99, 95%CI=0.73-1.32; EA female: OR=1.07, 95%CI=0.76-1.50; EA male: OR=0.93, 95%CI=0.65-1.32. In addition, when restricting the analysis to AA females younger than 45 years: n=1198, of which 186 had PTSD, who are likely to be pre-menopausal using an additive or dominant model: dominant model: OR=1.29, 95%CI=0.93-1.78.	In the unadjusted model, 'CC' genotype carriers showed a sma...... In the unadjusted model, 'CC' genotype carriers showed a small but non-statistically significant increased risk of PTSD compared with 'CG/GG' carriers. Our results were similar after adjusting for age at interview, age at worst trauma, trauma type, number of traumatic events and lifetime depression before PTSD. In pre-menopausal women. Menopausal status and type of menopause were assessed by biennial NHSII questionnaires.'CC' genotype did not significantly increase risk of PTSD in the pre-menopausal or natural menopause group. No significant association was observed in any of these four subgroups under either additive or dominant genetic models with respect to the G allele. In addition, there was no evidence of association whenrestricting the analysis to AA females younger than 45 years who are likely to be pre-menopausal using an additive or dominant model. More...	Non-significant
rs2267735	Current PTSD	ADCYAP1	Association for current PTSD: aOR for 'CC' carriers=0.94, 95% CI=0.64-1.39.	We also found no significant association for current PTSD, d...... We also found no significant association for current PTSD, defined as symptoms occurring within the past month. More...	Non-significant
rs2267735	Chronic PTSD	ADCYAP1	Association for chronic PTSD: aOR=1.14, 95%CI=0.84-1.55.	We also found no significant association for chronic PTSD, d...... We also found no significant association for chronic PTSD, defined as symptoms lasting more than 1 year. More...	Non-significant