Study Report

Study Information

Basic Info

Reference	Ressler, K. J.,2011 PMID: 21350482
Citation	Ressler, K. J., et al. (2011). "Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor." Nature 470(7335): 492-497.
Phenotype	PTSD diagnosis, PSS total score, PSS hyperarousal score, Fear Discrimination, Dark enhanced startle
Trauma	Various
Study Design	Case-control
Study Type	Candidate gene association study
Sample Size	255 cases, 543 controls
SNP/Marker Size	44 SNPs
Predominant Ethnicity	Black
Population	Case: 235 African Americans, 19 others. Control: 498 African Americans, 42 others
Gender	Case: 90 males, 165 females, Control: 205 males, 338 females
Age	Case: mean age=41.98 years, Control: mean age=39.71 years

Detail Info

Sample Diagnosis	DSM-IV
Related Diagnostic Tools	The Traumatic Events Inventory (TEI), The Traumatic Events Inventory (TEI), Beck Depression Inventory (BDI)
Sample Status	87.7% of the cases have current substance abuse, 96.8% of the control group have current substance abuse
Controls Exposed	NS
Replication Size	143 cases, 296 controls
Result Summary	Using a tag-SNP genetic approach (44 single nucleotide polymorphisms, SNPs) spanning the PACAP(ADCYAP1) and PAC1(ADCYAP1R1) genes, we find a sex-specific association with PTSD. rs2267735, a SNP in a putative estrogen response element within ADCYAP1R1, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 mRNA expression. Methylation of ADCYAP1R1 is also associated with PTSD (P-value< 0.001). These data suggest that perturbations in the PACAP/PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via estrogen regulation of ADCYAP1R1.
Potential Biomarker	ADCYAP1R1, PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.

Genetic result reported by this study

Normal genetic result reported by this study (count: 31)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs7786118	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.63, males: P-value=0.918	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs7784067	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.834, males: P-value=0.291	No significant result in females or males No significant result in females or males	Non-significant
rs10269014	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.228, males: P-value=0.701	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs10277350	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.86, males: P-value=0.135	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs741051	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.879, males: P-value=0.022	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs12670977	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.525, males: P-value=0.014	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs11979764	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.508, males: P-value=0.565	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs1541516	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.858, males: P-value=0.941	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs1541518	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.064, males: P-value=0.974	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs12670991	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.603, males: P-value=0.71	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs17159861	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.457, males: P-value=0.176	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267735	Fear Discrimination	ADCYAP1R1	In females: P-value<0.05	Fear Discrimination (CS+ Startle minus CS? Startle) is impai...... Fear Discrimination (CS+ Startle minus CS? Startle) is impaired in females with rs2267735 'CC' genotype. More...	Significant
rs17723231	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.466, males: P-value=0.288	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs1981701	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.729, males: P-value=0.021	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs7805043	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.995, males: P-value=0.483	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs7804302	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.48, males: P-value=0.226	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2041568	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.149, males: P-value=0.611	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs7804958	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.23, males: P-value=0.992	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267738	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.493, males: P-value=0.099	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267737	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.557, males: P-value=0.669	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267740	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.52, males: P-value=0.864	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267727	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.546, males: P-value=0.834	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267735	PTSD diagnosis	ADCYAP1R1	In original sample: females: P-value=0.0002, males: P-value=0.763. In a replicated sample: females: Wald X²=4.8, P-value=0.029, males: Wald X²=0.57, P-value=0.45. In a combined sample: females: Wald X²=18.4, P-value=0.000018, males: Wald X²=0.123, P-value=0.73.	Only the ADCYAP1R1 receptor SNP rs2267735 (in females; NS i...... Only the ADCYAP1R1 receptor SNP rs2267735 (in females; NS in males) remained significant after experiment-wide multiple correction for sex and 44 independent tests. The main effect of the SNP on PTSD diagnosis could be replicated in women and combining both samples increased the significance of the association. As in the discovery sample, no effects were observed in males. More...	Significant
rs2267733	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.11, males: P-value=0.78	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267735	PSS hyperarousal score	ADCYAP1R1	In females: P-value=0.0009, In a dominant/recessive model: P-value<=0.0001	Hyperarousal is the most robustly associated symptom with rs...... Hyperarousal is the most robustly associated symptom with rs2267735 genotype. In a dominant/recessive model, even after controlling for childhood trauma, adult trauma, and age, genotype predicts hyperarousal symptoms. More...	Significant
rs2267735	PSS total score	ADCYAP1R1	In females: P-value<=0.001, In a dominant/recessive model: P-value<=0.001	Total PTSD symptoms (PSS total) are differentially associate...... Total PTSD symptoms (PSS total) are differentially associated with rs2267735 genotype in females. In a dominant/recessive model, even after controlling for childhood trauma, adult trauma, and age, genotype predicts total PTSD symptoms. More...	Significant
rs4503014	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.843, males: P-value=0.366	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs10081254	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.239, males: P-value=0.845	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs2267735	Dark enhanced startle	ADCYAP1R1	In females: P-value<0.05	Dark enhanced startle (Startle Dark-Startle Light) is signif...... Dark enhanced startle (Startle Dark-Startle Light) is significantly increased in females with rs2267735 'CC'genotype. More...	Significant
rs10268647	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.794, males: P-value=0.935	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant
rs10241138	PTSD diagnosis	ADCYAP1R1	Females: P-value=0.948, males: P-value=0.883	No significant result in females or males after multiple cor...... No significant result in females or males after multiple corrections. More...	Non-significant