PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Almli, L. M.,2013 PMID: 23505260
Citation	Almli, L. M., et al. (2013). "ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females." Am J Med Genet B Neuropsychiatr Genet 162B(3): 262-272.
Phenotype	PTSD symptom severity
Trauma	Various
Study Design	Case-control
Study Type	Candidate gene association study, Gene-environment interaction study
Sample Size	1159 adults
SNP/Marker Size	1 SNP
Predominant Ethnicity	Black
Population	African American
Gender	301 males, 858 females
Age	18 years or older

Detail Info

Sample Diagnosis	DSM-IV
Related Diagnostic Tools	PTSD symptom scale (PSS), Beck depression inventory (BDI), Traumatic events inventory (TEI), Childhood trauma questionnaire (CTQ)
Sample Status	As a secondary analysis, we conducted a meta-analysis on a combined sample of African-Americans from the original sample (Ressler et al., 2011) plus the replication sample in order to tease apart the main and interacting effects of ADCYAP1R1 and variation in trauma load and/or child abuse on risk of PTSD in a larger overall high-risk sample. The replication sample set analyzed were unique SIDs and did not include any subjects included in the first manuscript. Only the African-American samples for whom we also had complete trauma load data (N=911) from the original manuscript (Ressler et al., 2011) were used in the meta-analysis.
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	Using linear regression models to test for association with PTSD symptom severity under an additive (allelic) model, we found a genotype x trauma interaction in females (P-value< 0.001), but not males (P-value> 0.1); however, there was no main effect of genotype as in our previous study. The observed interaction suggests a genetic association that increases with the degree of trauma exposure in females only. This interaction remained significant in females, but not males, after controlling for age (P-value< 0.001), income (P-value< 0.01), past substance abuse (P-value< 0.001), depression severity (P-value=0.02), or child abuse (P-value< 0.0005), and all five combined (P-value= 0.01). No significant effects of genotype (or interactions) were found when modeling depression severity when controlling for comorbid PTSD symptom severity (P-value > 0.1), demonstrating the relative specificity of this variant for PTSD symptoms. A meta-analysis with the previously reported African-American samples revealed a strong association between PTSD symptom severity and the interaction between trauma and genotype in females (N=1424, P-value< 0.0001).
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
rs2267735	PTSD symptom severity	ADCYAP1R1	X²=1.97, P-value>0.1	There was no statistically significant difference in the fre...... There was no statistically significant difference in the frequencies of each genotype between the sample sets. More...	Non-significant

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

Marker	Phenotype	Related Gene	Environment	Statistical Values	Author Comments	Marker's Category
rs2267735	PTSD symptom severity	ADCYAP1R1	Trauma Load	When stratifying by sex, in females (N=858) ADCYAP1R1 genotype x trauma interaction: t=3.46, P-value=0.0006, in males (N=301) ADCYAP1R1 genotype x trauma interaction: P-value=0.47. The genotype x trauma interaction in females adjusting for age: t= 3.44, P-value=0.0006, income: t= 3.21, P-value=0.001, past substance abuse: t=3.56, P-value=0.0004, depression severity: t=2.30, P-value=0.02, or childhood trauma load: t=3.76, P-value=0.0002, and all five:t=2.50, P-value=0.01. In the combined sample, trauma x genotype interaction in females (N=1424): t=4.30, P-value<0.0001; in males (N=646): P-value> 0.1, when adjusting for age: t=4.29, P-value< 0.0001, income: t=4.44, P-value< 0.0001, past substance abuse: t=4.31, P-value< 0.0001, depression severity: t=2.57, P-value=0.01, or childhood trauma load: t=4.16, P-value< 0.0001, and all five: t=2.85, P= 0.004.	We did find a genotype x trauma interaction that differed by...... We did find a genotype x trauma interaction that differed by sex. As shown in Figure 1B, the C allele is more associated with PTSD symptom severity for females with high trauma load. In males on the other hand, there was no ADCYAP1R1 genotype x trauma interaction. The genotype x trauma interaction in females remained when adjusting for age, income, past substance abuse, depression severity, or childhood trauma load, and all five. Moreover, when controlling for comorbid PTSD symptom severity, we did not find a significant association of ADCYAP1R1 genotype on depression severity nor a trauma x genotype interaction. The main finding of an ADCYAP1R1 genotype x trauma interaction on PTSD symptom severity was tested for statistical robustness and verified with permutation and bootstrapping methods. In the combined sample, we found a strong association between PTSD symptom severity and a trauma x genotype interaction in females but not males. Thus, at higher trauma levels, carriers of the C allele are associated with PTSD symptom severity. Again, the genotype x trauma interaction in females remained when adjusting for age, income, past substance abuse, depression severity, or childhood trauma load, and all five. More...	Significant