PTSDgene database

Pathway Enrichment Analysis Protein-Protein Interaction Analysis

Study Report

Study Information

Basic Info

Reference	Kimbrel, N. A.,2015 PMID: 26184988
Citation	Kimbrel, N. A., et al. (2015). "Effect of genetic variation in the nicotinic receptor genes on risk for posttraumatic stress disorder." Psychiatry Res 229(1-2): 326-331.
Phenotype	PTSD
Trauma	Various
Study Design	Case-control
Study Type	Candidate gene association study, Gene-environment interaction study
Sample Size	925 NHB participants and 743 NHW participants (total N=1668)
SNP/Marker Size	77 SNPs for NHB sample and 33 SNPs remained in the NHW sample.
Predominant Ethnicity	Black, Caucasian
Population	925 non-Hispanic Blacks (NHB) and 743 non-Hispanic Whites (NHW)
Gender	In NHB cases: 69.5% males; in NHB controls, 70.6% males; in NHW cases, 85.8% males, in NHW controls, 85.5% males.
Age	In NHB cases: mean age=38.7 years, SD=9.8; in NHB controls, mean age=39.4 years, SD=9.6; in NHW cases, mean age=35.2 years, SD=9.6, in NHW controls, mean age=37.2.

Detail Info

Sample Diagnosis	DSM-IV, DSM-IV-TR
Related Diagnostic Tools	The PDMH study used the Structured Clinical Interview for DSM-IV (SCID; First et al., 1994) to diagnose PTSD, whereas the Clinician-Administered PTSD Scale (CAPS; Blake et al., 1995) was used in the TSHG study. Traumatic Life Events Questionnaire (TLEQ; Kubany et al., 2000). Scores on the Davidson Trauma Scale (DTS; Davidson et al., 1997) were used to categorize participants as either cases (DTS>=75) or controls (DTS<=24) in the small number of instances (n=91) where neither SCID nor CAPS data was available.
Sample Status	Participants were drawn from the VA Mid-Atlantic Mental Illness Research, Education and Clinical Center (MIRECC) Post-Deployment Mental Health (PDMH) Study and the Traumatic Stress and Health Genetics (TSHG) Study at the Durham VA and Duke University Medical Center. The PDMH Study is a registry study of Veterans who served in the United States military since September 11, 2001. The TSHG study is a genetic study of PTSD that recruited participants from a variety of other trauma research studies at the Durham VA and Duke University Medical Center. Whereas the PDMH is restricted to Iraq/Afghanistan-era Veterans, the TSHG includes Veterans from a variety of eras as well as community civilians who agreed to donate a blood sample for genetic analyses.
Controls Exposed	Not mentioned.
Replication Size	None
Result Summary	No significant main effects or single nucleotide polymorphism (SNP) x smoking interactions were observed among NHB participants; however, among NHW participants, a novel association between rs12898919 in the cholinergic receptor nicotinic alpha-5 (CHRNA5) gene and PTSD was observed. No other significant main effects or SNP x smoking interactions were identified among NHW participants. While preliminary, these findings provide continued support for the hypothesis that the CHRNA5 gene is associated with increased risk for PTSD. Limitations of the present study include cross-sectional design, relatively small sample sizes for genetic research, use of self-report to assess smoking status, and use of different methods to diagnose PTSD. Additional research in other samples of trauma-exposed participants is needed to identify the specific functional variant(s) responsible for the association observed between CHRNA5 and PTSD risk in the present study.
Potential Biomarker	None

Genetic result reported by this study

Normal genetic result reported by this study (count: 13)

Marker	Phenotype	Related Gene	Statistical Values	Author Comments	Marker's Category
rs2565067	PTSD	CHRNA2	In the NHW sample, main effect: P-value=0.9635.	No main effect was statistically significant among NHW parti...... No main effect was statistically significant among NHW participants. More...	Non-significant
rs12898919	PTSD	CHRNA5	In the NHW sample, 95% confidence interval (CI)=1.44-3.83, P-value=0.0006114, an ad hoc allele test(C allele vs. G allele): 95%CI= 1.380-3.578, P-value=0.0010.	A different SNP (rs12898919) in the CHRNA5 gene provided evi...... A different SNP (rs12898919) in the CHRNA5 gene provided evidence for a main effect on PTSD risk in the NHW sample, and this association met correction for multiple testing. Specifically, we found that rs12898919 of the CHRNA5 gene was significantly associated with having a current PTSD diagnosis, such that for each additional C allele, the odds of PTSD increased by 2.35. An ad hoc allele test was conducted to ensure the genotype of the one participant that was homozygous for the C allele was not driving the observed association with this SNP. The association remained significant in the allele test (C allele vs. G allele), such that those with the C allele were 2.22 times as likely as those with the G allele to have PTSD. More...	Significant
rs1316971	PTSD	CHRNA4	In the NHW sample, main effect: P-value=0.003377.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs80087508	PTSD	CHRNA5	In the NHB sample, main effect: P-value=0.01196.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs8036584	PTSD	CHRNA7	In the NHW sample, main effect: P-value=0.005739.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs10104133	PTSD	CHRNA2	In the NHB sample, main effect: P-value=0.7681.	No main effect was statistically significant among NHB parti...... No main effect was statistically significant among NHB participants. More...	Non-significant
rs16969968	PTSD	CHRNA5	Main genetic effects among NHB participants: P-value=0.0858, among the NHW participants: P-value=0.6153.	No main genetic effects were statistically significant among...... No main genetic effects were statistically significant among NHB participants at the multiple testing threshold of 0.0007 (Table 2). This SNP was also not associated with PTSD among the NHW participants. More...	Non-significant
rs60646603	PTSD	CHRNA2	In the NHB sample, main effect: P-value=0.03028.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs62516743	PTSD	CHRNA3	In the NHW sample, main effect: P-value=0.7071.	No main effect was statistically significant among NHW parti...... No main effect was statistically significant among NHW participants. More...	Non-significant
rs75431302	PTSD	CHRNA3	In the NHB sample, main effect: P-value=0.0908.	No main effect was statistically significant among NHB parti...... No main effect was statistically significant among NHB participants. More...	Non-significant
rs588765	PTSD	CHRNA5	In the NHW sample, main effect: P-value=0.02006.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs74572794	PTSD	CHRNA6	In the NHW sample, main effect: P-value=0.1012.	No main effect was statistically significant among NHW parti...... No main effect was statistically significant among NHW participants. More...	Non-significant
rs73679204	PTSD	CHRNA2	In the NHB sample, main effect: P-value=0.01487.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant

Gene * Environment result reported by this study (count: 13)

Marker	Phenotype	Related Gene	Environment	Statistical Values	Author Comments	Marker's Category
rs16969968	PTSD	CHRNA5	Smoking status	GxE interactions among NHB participants: P-value=0.4467, among the NHW participants: P-value=0.172.	No GxE interactions were statistically significant among NHB...... No GxE interactions were statistically significant among NHB participants or among the NHW participants. More...	Non-significant
rs74572794	PTSD	CHRNA6	Smoking status	GxE interactions among NHW participants: P-value=0.0152.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs75431302	PTSD	CHRNA3	Smoking status	GxE interactions among NHB participants: P-value=0.039.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs73679204	PTSD	CHRNA2	Smoking status	GxE interactions among NHB participants: P-value=0.1744.	No GxE interactions were statistically significant among NHB...... No GxE interactions were statistically significant among NHB participants. More...	Non-significant
rs1316971	PTSD	CHRNA4	Smoking status	GxE interactions among NHW participants: P-value=0.6343.	No GxE interactions were statistically significant among NHW...... No GxE interactions were statistically significant among NHW participants. More...	Non-significant
rs12898919	PTSD	CHRNA5	Smoking status	GxE interactions among NHW participants: P-value=0.4988.	No GxE interactions were statistically significant among NHW...... No GxE interactions were statistically significant among NHW participants. More...	Non-significant
rs60646603	PTSD	CHRNA2	Smoking status	GxE interactions among NHB participants: P-value=0.7831.	No GxE interactions were statistically significant among NHB...... No GxE interactions were statistically significant among NHB participants. More...	Non-significant
rs588765	PTSD	CHRNA5	Smoking status	GxE interactions among NHW participants: P-value=0.04947.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs62516743	PTSD	CHRNA3	Smoking status	GxE interactions among NHW participants: P-value=0.03093.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs80087508	PTSD	CHRNA5	Smoking status	GxE interactions among NHB participants: P-value=0.9147.	No GxE interactions were statistically significant among NHB...... No GxE interactions were statistically significant among NHB participants. More...	Non-significant
rs2565067	PTSD	CHRNA2	Smoking status	GxE interactions among NHWB participants: P-value=0.007639.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant
rs8036584	PTSD	CHRNA7	Smoking status	GxE interactions among NHW participants: P-value=0.5851.	No GxE interactions were statistically significant among NHW...... No GxE interactions were statistically significant among NHW participants. More...	Non-significant
rs10104133	PTSD	CHRNA2	Smoking status	GxE interactions among NHB participants: P-value=0.04795.	Nominally significant associations (p<.05) were observed, bu...... Nominally significant associations (p<.05) were observed, but it didn't met multiple-testing threshold. More...	Significant