SNP Report

Basic Info

Name	rs2267735 dbSNP Ensembl
Location	7:31095890 - 31095890(+)
Variant Seq	G
Ancestral Allele	C
Ref Seq	C
Minor Allele Frequence	0.448482
Annotation	intron_variant
Variant Effect	intron_variant(ENST00000409363, ENST00000409489, ENST00000304166, ENST00000436116, ENST00000614107, ENST00000396211)
SIFT Annotation	deleterious
SIFT Variant Effect	deleterious(ENST00000436116, ENST00000614107, ENST00000304166, ENST00000409489, ENST00000396211, ENST00000409363)
PolyPhen Annotation	probably_damaging; possibly_damaging
PolyPhen Variant Effect	probably_damaging(ENST00000409489); possibly_damaging(ENST00000436116, ENST00000614107, ENST00000304166, ENST00000396211, ENST00000409363)
rSNP?	Yes Link in rVarBase
Related Regulatory Elements	n/a
Chromatin State	Weak transcription;Strong transcription
No. of Marker's Association Results	22 (Positive: 7; Negative: 15; Trend: 0)
Source	Literature

SNP related association results

Normal genetic study related association results (count: 22)

Reference	Phenotype	Statistical Values	Author Comments	Marker's Category
Wang, L.,2013	Anxious arousal symptoms	CC carriers vs G allele carriers: In women: B=0.06, P-valu...... CC carriers vs G allele carriers: In women: B=0.06, P-value=0.39, In men: B=0.18, P-value=0.08 More...	No association was found. No association was found.	Non-significant
Wang, L.,2013	Avoidance symptoms	CC carriers vs G allele carriers: In women: B=0.02, P-valu...... CC carriers vs G allele carriers: In women: B=0.02, P-value=0.73, In men: B=0.02, P-value=0.84 More...	No association was found. No association was found.	Non-significant
Chang, S. C.,2012	Chronic PTSD	Association for chronic PTSD: aOR=1.14, 95%CI=0.84-1.55. 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
Chang, S. C.,2012	Current PTSD	Association for current PTSD: aOR for 'CC' carriers=0.94, 9...... Association for current PTSD: aOR for 'CC' carriers=0.94, 95% CI=0.64-1.39. More...	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
Ressler, K. J.,2011	Dark enhanced startle	In females: P-value<0.05 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
Rothbaum, B. O.,2014	Diagnosis of PTSD at week 12	Intervention group: X²= 5.85, P-value=0.02, Asse...... Intervention group: X²= 5.85, P-value=0.02, Assessment group: X²= 0.04, P-value=0.84 More...	Subjects with the risk genotype (CC) were more likely to be ...... Subjects with the risk genotype (CC) were more likely to be diagnosed with PTSD at week 12 (87.5%) compared to carriers of the low-risk allele (12.5%) if they were assessed-only, whereas there was no difference between genotype risk groups in the intervention cohort. More...	Significant
Wang, L.,2013	Dysphoric arousal symptoms	CC carriers vs G allele carriers: In women: B=0.03, P-valu...... CC carriers vs G allele carriers: In women: B=0.03, P-value=0.63, In men: B=-0.10, P-value=0.32 More...	No association was found. No association was found.	Non-significant
Wang, L.,2013	Emotional numbing symptoms	CC carriers vs G allele carriers: In women: B=0.17, P-valu...... CC carriers vs G allele carriers: In women: B=0.17, P-value=0.01, In men: B=0.05, P-value=0.63 More...	Only emotional numbing symptoms were associated with rs22677...... Only emotional numbing symptoms were associated with rs2267735 in women, but not men. The rs2267735 'CC' genotpe also was associated with only emotional numbing symptoms in women after controlling for demographic variables. More...	Significant
Ressler, K. J.,2011	Fear Discrimination	In females: P-value<0.05 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
Uddin, M.,2013	Past month PTS severity	Linear regression model: P-value=0.805. Linear regression model: P-value=0.805.	There was no significant association between ADCYAP1R1 genot...... There was no significant association between ADCYAP1R1 genotype and past month PTS severity in the linear regression analyses. More...	Non-significant
Uddin, M.,2013	Past month PTSD	Logistic regression analyses of the effect of ADCAYP1R1 geno...... Logistic regression analyses of the effect of ADCAYP1R1 genotype and CM on PTSD, controlling for age, race, and past month depression: ADCYAP1R1 genotype P-value=0.60. More...	There was no significant association between ADCYAP1R1 genot...... There was no significant association between ADCYAP1R1 genotype and past month PTSD in the logistic regression analyses. More...	Non-significant
Ressler, K. J.,2011	PSS hyperarousal score	In females: P-value=0.0009, In a dominant/recessive model: ...... In females: P-value=0.0009, In a dominant/recessive model: P-value<=0.0001 More...	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
Ressler, K. J.,2011	PSS total score	In females: P-value<=0.001, In a dominant/recessive model: ...... In females: P-value<=0.001, In a dominant/recessive model: P-value<=0.001 More...	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
Chang, S. C.,2012	PTSD	NHSII: In the unadjusted model, 'CC' genotype carriers comp...... 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. More...	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
Ressler, K. J.,2011	PTSD diagnosis	In original sample: females: P-value=0.0002, males: P-val...... 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. More...	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
Chang, S. C.,2012	PTSD symptom severity	Unadjusted P-value=0.48-0.98. 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
Almli, L. M.,2013	PTSD symptom severity	X²=1.97, P-value>0.1 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
Chang, S. C.,2012	PTSD symptom subscale scores	Unadjusted P-value=0.48-0.98. 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
Wang, L.,2013	PTSD symptoms	CC carriers vs G allele carriers: In women: B=0.12, P-valu...... CC carriers vs G allele carriers: In women: B=0.12, P-value=0.08, In men: B<0.01, P-value=0.98 More...	The rs2267735 'cc' genotype was not associated with total PT...... The rs2267735 'cc' genotype was not associated with total PTSD symptoms, the association in women was marginally significant. More...	Non-significant
Rothbaum, B. O.,2014	PTSD symptoms at week 4	Intervention group: P-value=0.22, Assessment group: P-valu...... Intervention group: P-value=0.22, Assessment group: P-value=0.32 More...	There were no significant differences at the 4-week time poi...... There were no significant differences at the 4-week time point for the intervention and the assessment groups. More...	Non-significant
Wang, L.,2013	Reexperiencing symptoms	CC carriers vs G allele carriers: In women: B=0.11, P-valu...... CC carriers vs G allele carriers: In women: B=0.11, P-value=0.09, In men: B=-0.07, P-value=0.52 More...	No association was found. No association was found.	Non-significant
Chang, S. C.,2012	Total number of PTSD symptoms	Unadjusted P-value=0.48-0.98. 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

G*E study related association result (count: 4)

Reference	Phenotype	Environment	Statistical Values	Author Comments	Marker's Category
Uddin, M.,2013	Correlations between chlidhood maltreatment and past month PTS severity	Childhood maltreatment (CM)	CC versus GG group: z-value=2.071, P-value< .05; CC versus C...... CC versus GG group: z-value=2.071, P-value< .05; CC versus CG group: z-value=2.868, P-value< .01. More...	Stratification by ADCYAP1R1 genotype showed that these corre...... Stratification by ADCYAP1R1 genotype showed that these correlations were significant only among genotypes containing the "C" allele. Moreover, correlation coefficients were significantly higher in the CC versus GG group and in the CC versus CG group. More...	Significant
Uddin, M.,2013	Past month PTS severity	Childhood maltreatment (CM)	Linear regression model: P-value=0.037. Linear regression model: P-value=0.037.	Results were similar when PTS severity used as outcomes with...... Results were similar when PTS severity used as outcomes with PTSD as outcomes. More...	Significant
Uddin, M.,2013	Past month PTSD	Childhood maltreatment (CM)	Logistic regression analyses of the effect of ADCAYP1R1 geno...... Logistic regression analyses of the effect of ADCAYP1R1 genotype and CM on PTSD, controlling for age, race, and past month depression: results from interaction effect analyses P-value=0.029, permutation P-value=0.030. More...	Results from interaction effect analyses showed that partici...... Results from interaction effect analyses showed that participants with one versus no "C" alleles at the ADCAYP1R1 rs2267735 locus showed a 17% increased odds of past month PTSD for every one-unit increase in CM score in the logistic regression model. Analyses based on African-American participants only showed similar results. More...	Significant
Almli, L. M.,2013	PTSD symptom severity	Trauma Load	When stratifying by sex, in females (N=858) ADCYAP1R1 genoty...... 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. More...	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

SNP related genes (count: 2)

Approved Symbol	Approved Name	Location	No. of Association Results (Positive/Negative/Trend)
ADCYAP1	adenylate cyclase activating polypeptide 1 (pituitary)	18p11	6(0/6/0)
ADCYAP1R1	adenylate cyclase activating polypeptide 1 (pituitary) receptor type I	7p14.3	19(8/11/0)

SNPs in LD with rs2267735 (count: 2)

The LD data used here is based on 1000 Genome Phase I. LD SNP pairs were selected with a threshold r²<=0.8.

Literature-origin SNPs (count: 0)

LD-proxies (count: 2)

rs_ID	Literature-origin SNPs with LD	Annotation	r²[population]
rs2267734	rs2267735	intron_variant	0.9687[EUR]
rs2267732	rs2267735	intron_variant	0.8472[ASN]

SNP related eQTL (count: 1)

Gene Symbol	Gene Existed in PTSDgene?	Tissue	Trans/Cis	Source
LRRC37A4P	No	Adipose Subcutaneous	cis	GTEx