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Table 1 Demographic information, results and conclusions for GxE Studies of PTSD

From: Considering trauma exposure in the context of genetics studies of posttraumatic stress disorder: a systematic review

Reference (year) Sample size (% PTSD Cases)a Mean age (SD) Race Primary trauma type Issue of multiple traumas addressed? Gene Significant main effect of trauma? Significant main effect of gene? GxE interaction? General conclusions
Studies of Child Trauma on Child PTSD (2)
Amstadter et al. (2011) 103; PTSD-RI M= 24.09 (12.2) 14.63 (3.2) 40.8% EA; 45.6% AA; 13.6% O Physical injury NRb CRHR1 Yes Yes NR rs12944712 was significantly related to higher acute PTSD Sxs and increasing trajectory of Sxs over time.
Drury et al. (2009) 88 (NR) 3-6(NR) 56% AA; 40% EA Hurricane Katrina NR DAT1 NR Yes NR The 9 allele increased risk of PTSD—both in the form of total and Criterion D Sxs.
Studies of Adults with History of Child and/or Adult Trauma on Adult PTSD (4)
Binder et al. (2008)` 900c 40.8 (13.8) 95.2% AA; Child abuse and non-child abuse Yes FKBP5 Yes No Yes Significant interaction between FKBP5 polymorphisms and child abuse found for adult PTSD Sxs. The interaction for adult trauma was not significant.
2.2% EA;
0.6% L;
0.1% A;
0.9% Mixed;
1.0% Other
Nelson et al. (2009) 259 (17.8% LT) NR NR Child abuse NR GABRA2 NR No Yes Interactions b/w child trauma and SNP genotype provide consistent support for GxE interactions involving child trauma and SNP genotype. When separate variables were coded for the presence of one or two risk-associated alleles, significant Gx E interactions are only found for homozygous individuals.
Xie et al. (2010) 2427 (14.0% LT) 38.6 (10.8) 47.1% EA; 52.9% AA Child adversity Yes FKBP5 Yes No Yes In AAs, the interaction between child adversity and all 4 FKBP5 SNPs were associated with PTSD. SNP rs9470080 had strongest conditional effect; for AAs without child adversity, those homozygous for T allele had lowest risk of PTSD, while homogygotes with adversity had highest risk.
Xie et al. (2009) 1252 (18.3% LT) 38.9( 11) 46.5% EA; 53.5% AA Both Yes SLC6A4 Yes No Yes 5-HTTLPR polymorphism alone did not predict PTSD; however it interacted with adult traumatic events and child adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure.
Studies of Adults which Assessed Adult Trauma (22)
Amstadter et al. (2009) 607 (3.6%) 22.6% ≤ 59 90% EA; 3.9% AA; 3.9% L; 1.7% Other; 0.5% Missing 2004 FL hurricanes Yes RGS2 No No Yes GxE interaction such that rs4606 moderated risk of PTSD Sxs under high E stress and low social support.
Both LT and CT Sxs asses’d
77.4% ≥ 60
Kolassa et al. (2010a) 424 (80.2% LT; 48.8% CT) 34.8 (5.8) 100% Hutu or Tutsi Rwandan genocide Yes COMT Yes, LT PTSD No, for LT and CT PTSD Yes, LT PTSD COMT genotype affected PTSD such that met/met homozygotes had higher risk for PTSD than those with Val allele independent of severity of traumatic load.
Kolassa et al. (2010b) 408 (81.1% LT) 34.68 (5.9) 100% Rwandan refugees Rwandan genocide Yes SLC6A4 Yes , LT PTSD Yes , LT PTSD Yes , LT PTSD Probability of developing PTSD was 100% for s homozygotes and there was no dose–response relationship between trauma and PTSD. However, when trauma approached extreme levels, genotype effect disappeared and PTSD approached 100%.
Kilpatrick et al. (2007) 589 (3.2% CT) 22.6%≤ 59 90% EA; 3.9% AA; 3.9% L; 1.7% Other; 0.5% Missing 2004 FL hurricanes Yes SLC6A4 No No Yes 5-HTTLPR increased risk of PTSD under low social support condition.
76.6% ≥ 60
Thakur et al. (2009) 41 (59% “acute” PTSD) 32 (NR) 95% EA; 5% Other MVAd Yes SLC6A4 NR Yes NR Higher chronic PTSD was found in ll genotypes than sl and ss genotypes.
Dragan al. (2009) 107 (22.4% CT) 35.57 (12.89) NR Polish flood Yes DRD4 Yes Yes No At least 1 copy of DRD4 long allele related to higher total PTSD and Avoidance/Numbing Sxs.
Comings et al. (1996) 56 (66%*) 43.6 (NR) 100% EA Vietnam War No DRD2 NR Yes NR 59.5% of those with PTSD had D 2 A1 allele; of the group that did not have PTSD, only 5.3% had D 2 A1 allele.
Bachmann et al. (2005) 160 (73.8%*) 55.7 (4.2) NR Vietnam War No GCCR NR No NR N363S and Bcll GR polymorphisms not more frequent in PTSD patients than controls.
Gelernter et al. (1999) 139 (37.4%*) With PTSD: 44.6 (3.6) 100% EA Vietnam War No DRD2 NR No NR No allelic association between DRD2 TaqI “A” system alleles and PTSD.
Without PTSD: NR
Grabe et al. (2009) 1,663 (4.03% LT) With ≥ 1 traumatic experience: 57.6 (15.6); without traumatic experience: 50.0 (13.3) 100% EA Community based sample; variety of events Yes SLC6A4 Yes Yes Yes GxE interaction found between high expression of L A allele and frequent trauma.
Koenen et al. (2009) 590 (3.2% CT) <60 = 22.7% 90.7% EA; 9.5% Other 2004 FL hurricanes NR SLC6A4 Yes No Yes County-level crime and employment rate modified association between genotype and PTSD risk. The s’ allele associated with decreased risk in low-risk environments and increased risk in high-risk environments.
Mellman et al. (2009) 118 (47% LT) 39.9(16.3) NR Various NR SLC6A4 NR Yes NR 5HT2A G allele significantly associated with PTSD.
Mustapic et al. (2007) 167 (85% CT and LT) With PTSD: 40.3 (7.2); Without PTSD 38.12 (4.2) 100% Croatian Caucasian Combat-related trauma No DBH NR Yes NR PTSD associated with significantly lower plasma DBH activity in those carrying CC genotype.
Sayin et al. (2010) 77 (23.3% CT and 50.0% LT) NR NR Mild physical trauma NR SLC6A4 Yes No No Having L allele for 5-HTT gene- linked polymorphic region may cause milder hyperarousal symptoms in those patients who have developed PTSD.
Segman et al. (2002) 206 (50.5% CT) With PTSD: 39.7 (11.7); Without PTSD: 33.9 (10.2) 100% Jewish of definite Ashkenazi or non-Ashkenazi origin Various (e.g., road accidents, terrorism) NR DAT1 NR Yes NR The nine repeat allele at the DAT1 locus associated with increased risk for PTSD.
Bailey et al. (2010) 200 (36.5%*e) NR 100% Armenian 1988 Armenian Earthquake NR DRD2, DAT1 NR No NR Neither DRD2 nor DAT1 associated with PTSD.
Sarapas et al. (2011) 40 (50% total; both CT and LT assessed) With PTSD: 57.30 (13.2); Without PTSD: 51.20 (15.9) 100% EA 9/11 attacks Yes FKBP5 Yes, child trauma No NR Comparison of LT versus CT PTSD identified overlapping genes with altered expression suggesting enduring markers, while some markers present only in CT PTSD may reflect state measures. As a follow-up, direct comparisons of expression in CT PTSD, LT-only PTSD, and control groups identified FKBP5 and MHC Class II as state markers, and also identified several trait markers. An analysis of indirect effects revealed that homozygosity for any of 4 PTSD risk-related polymorphisms at FKBP5 predicted FKBP5 expression, which mediated indirect effects of genotype on plasma cortisol and PTSD severity.
Yes, other trauma
Valente et al. (2011a) 99 (66.5%*) With PTSD: 37.9 (8.7); Without PTSD: 44 (13.8) NR Urban violence Yes COMT No, child trauma Yes NR Found significant association (between met allele and PTSD in victims of violence
Valente et al. (2011b) 99 (66.5%*) With PTSD: 37.9 (8.7); Without PTSD: 44 (13.8) NR Being victim of an urban violence that could be characterized as criterion A Yes BDNF, DAT1, SLC6A4 No Yes, DAT1 NR Only the nine repeat allele of the DAT1 was associated with an increased risk of PTSD after being exposed to urban violence.
No, SLC6A4
Hauer et al. (2011) 126 (11.9% CT) Homozygotes: 67.1(10.8); Heterozygotes: 65.8(9.3) NR Cardiac surgery NR GCCR No Yes NR Homozygous Bcll *G carriers at an increased risk for PTSD stress.
Ressler et al. (2011) NR NR Majority AA NR NR PACAP, PAC1 NR Yes, women only NR Alterations in the PACAP–PAC1 pathway involved in abnormal and sex-specific stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1.
Tang et al. (2010) 227 (30.4% CT) 43.9 (12.8) 100% AA NR NR DBH ME for adult; No ME for child No NR No relationship between sDβH and PTSD (i.e., Sx or Dx)
  1. a In the absence of information on percentage of PTSD in sample, M(SD) of PTSD symptoms provided, when available.
  2. b NR = Not reported.
  3. c Overall M(SD) not reported.
  4. d MVA = Motor vehicle accident.
  5. e* = Authors did not distinguish between lifetime (LT) and current (CT) PTSD.