Table 2.
Genetic association studies of PTSD organized by neurobiological system
| Reference (year) |
Trauma type |
Cases, n (% male) |
Mean age, y (SD) |
Case ascertainment | Controls, n (% male) |
Mean age, y (SD) | Control exposed |
Comorbid, current and history |
Nation/ ethnicity |
Gene and dbSNP | Finding | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases | Controls | |||||||||||
| [12] (1991) | “Severe” combat | 35 (100) | NR | Setting: VA clinic; method: NR; time from E: NR | 314 (100) | NR | No | Yes | Yes | United States/NHW | DRD2; rs1800497 | Excess T in PTSD cases (P=0.007); P=0.0008 when controls screened for alcoholism |
| [13] (1996) | Combat | 37 (100) | ~44 | Setting: VA clinic; method: SI: DSM-III; time from E: NR | 19 (100) | ~44 | Yes | Yes | Yes | United States/NHW | DRD2; rs1800497 | Excess T in PTSD cases (P=0.00001); T positively associated with symptoms |
| [14] (1999) | Combat | 52 (100) | 45 (4) | Setting: VA clinic; method: SI: SCID, SADS-L; time from E: NR | 87 (100) | NR | No | Yes | No | United States/NHW | DRD2; rs1800497, rs1079597, rs1800498 | No significant association between SNPs/haplotypes and PTSD |
| [15] (2002) | Combat | 91 (100) | 52 (1) | Setting: inpatient unit; method: SI: DSM-IV; time from E: NR | 51 (35) | 39 (2) | No | Yes | NR | Australia/NHW | DRD2; rs1800497 | Excess T only in PTSD cases with harmful (≥60 g) drinking (P< 0.001); T associated with alcohol consumption among cases |
| [16] (2009) | Combat | 127 (100) | NR | Setting: hospital; method: SI: DSM-IV; time from E: “decades” | 228 (NR) | NR | NSF | No | NR | Australia/NHW | DRD2; rs1800497, rs6277, rs1799732 | Excess rs6277 C in PTSD (P=0.021) |
| [19] (2009) | Flood | 24 (~47) | ~36 | Setting: epidemiologic exposure; method: SI: PTSD-F, PTSD-C, DSM-IV symptoms; time from E: 3 mo | 83 (~47) | ~36 | Yes | NR | NR | Poland/NR | DRD4; VNTR (exon 3) | “Long” (7- and 8-repeat carriers) predicted more intense PTSD symptoms (P=0.048), more specifically those related to avoidance and numbing (P=0.035); no association with PTSD risk |
| [17] (2002) | Various | 102 (56) | 40 (12) | Setting: PTSD research studies/medical health clinic; method: SI: CAPS, SCID; time from E: “chronic” | 104 (47) | 34 (10) | Yes | No | No | Israel/Ashkenazi and non- Ashkenazi | DAT1; VNTR (3 UTR) | Excess 9-repeat in PTSD cases (P=0.012) |
| [18] (2009) | New Orleans Hurricane Katrina/2005 | Total: 88 (59) | 3–6 | Setting: epidemiologic exposure; method: SSI: preschool age psychiatric assessment, DSM-IV; time from E: <3 y | Total: 88 (59) | 3–6 | Yes | No | No | United States/AA; United States/NHW; United States/other | DAT1; VNTR (3 UTR) | Significant difference in PTSD risk by genotype classification (P<0.05, 9/9 highest risk); 9 carriers exhibited greater total symptoms compared with 10/10 genotype (driven by criterion D: arousal) |
| [21] (2005) | Various | 100 (43) | 35 (10) | Setting: medical health clinic; method: SI: DSM-IV; time from E: NR | 197 (39) | 35 (11) | NSF | No | No | Korea/Korean | SLC6A4; rs4795541 | Excess s allele in PTSD cases (P=0.04) |
| [22] (2010) | Rwandan civilian war (36 war/nonwar events) | 331 (~53) | ~35 | Setting: epidemiologic exposure; method: SI: PDS, DSM-IV; time from E: 13 y postwar | 77 (~53) | ~35 | Yes | No | No | Rwanda/NR | SLC6A4; rs4795541, rs25531 | s/s associated with increased risk of lifetime PTSD (P=0.008); no gene– environment (number of TE types, or time since trauma) interaction; significant dose–response between number of event types and lifetime PTSD among s/l and l/l, but not among s/s (interaction not significant); no association with current PTSD or remission from lifetime PTSD |
| [23••] (2007) | Hurricane 2005 (Florida) | 19 (32) | Adults | Setting: epidemiologic exposure; method: telephone interview, National Women’s Study PTSD module; time from E: 6 mo (“current”) | 570 (37) | Adults | Yes | Yes | Yes | United States/NHW; United States/AA, HW, As | SLC6A4; rs4795541, rs25531 | Significant association between s/s genotype and PTSD in adults with high hurricane exposure and low social support prior to hurricane (P<0.03 for interaction); similar effect pattern observed for MD |
| [24••] (2009) | Hurricane 2004 (Florida); various | 19 (32) | Adults | Setting: epidemiologic exposure; method: telephone interview, National Women’s Study PTSD module; time from E: 6 mo (“current”) | 571 (36) | Adults | Yes | Yes | Yes | United States/NHW; United States/AA, HW, As | SLC6A4; rs4795541, rs25531 | Significant interaction between genotype and crime rate (P=0.03) or unemployment (P=0.007) for risk of PTSD; s allele was associated with decreased risk of PTSD in low-risk environments (low crime/unemployment) and increased risk of PTSD in high-risk environments |
| [25] (2007) | Various | 107 (42) | 34 (10) | Setting: medical center; method: SI: DSM-IV, SCID-Kor; time from E: NR (“chronic”) | 161 (32) | 32 (10) | NSF | No | No | Korea/Korean | 5-HTR2A; rs6311 | Excess GG in female PTSD case (P=0.04) |
| [26•] (2009) | Motor vehicle accidents, other trauma | 24 (~46) | ~30 | Setting: prospective study of emergency department trauma patients (convenience sample); method: SI: development and persistence and SI, PDI, PDEQ, CAPS, DSM-IV, MINI; time from E: 1-mo and 12-mo follow-up for remission (acute) or persistence (chronic) | 17 (~46) | ~30 | Yes | NR | NR | United States/NHW; United States/other | SLC6A4; rs4795541 | At 12 mo, excess l/l in chronic PTSD vs non-PTSD and acute cases (P=0.052) |
| [27] (2009) | Various | 229 (42) | 39 (10) | Setting: hospital/medical health clinic; method: SSADDA, includes PTSD interview; time from E: “lifetime” | 1023 (54) | 39 (11) | Yes | Yes | Yes | United States/NHW; United States/AA | SLC6A4; rs4795541, rs25531 | No main effect of gene/variant on PTSD risk; gene–adult trauma interaction: NHW, P=0.03, AA, P=0.04; gene– child adversity interaction: NHW, P=0.02, AA, P=0.16; highest risk group: “ss” and event; gene–(adult trauma and child adversity) interaction: NHW, P=0.002, AA, P=0.04 |
| [28] (2009) | Various | 67 (36) | 58 (17) | Setting: study of health in Pomerania; method: SCID; time from E: “lifetime” | 1596 (51) exposed; 1382 (46) not exposed | 58(16); 50 (13) | NSF | Yes | Yes | German/NHW | SLC6A4; rs4795541, rs25531 | La increased risk of PTSD (P=0.009); in individuals with more than 3 traumatic life events, an additive interaction was found with the La allele conferring risk (P<0.05 for interaction) |
| [29] (2009) | Various | 55 (24) | 40 (16) | Setting: university clinics; method: CAPS for PTSD, SCID for MD and other psychotic disorders, life event checklist; time from E: NR (“lifetime”) | 63 (45) | 40 (17) | Yes | Yes | Yes | United States/AA | SLC6A4; rs4795541, rs25531; 5-HT2A; rs6311 | No significant association between SLC6A4 SNPs and PTSD; excess rs6311 G allele in PTSD cases (P=0.008) |
| [30] (2010) | Physical trauma, stroke | 29 (38) | NR | Setting: emergency department; method: telephone interview, CAPS; time from E: assessed 6 mo after trauma (“lifetime”) | 48 (75) | NR | Yes | Yes | Yes | Turkey/NHW | SLC6A4; rs4795541, rs57098334 | No association with lifetime PTSD; L carriers associated with milder hyperarousal symptoms (P=0.05), and carriers of “12” associated with more severe avoidance symptoms (P<0.05); S carriers related to more severe PTSD (P=0.05) |
| [38] (2008) | Various | 762 (~43) | ~41 (14) | Setting: hospital/medical health clinic; method: PSS, CAPS; time from E: NR (“lifetime”) | – | – | – | Yes | – | United States/AA; United States/other | FKBP5; rs3800373, rs992105, rs9296158, rs737054, rs1360780, rs1334894, rs9470080, rs4713916 | rs3800373 (risk C), rs9296158 (A), rs1360780 (T), and rs9470080 (T) each significantly interacted with severity of child abuse in prediction of adult PTSD symptoms (P< 0.0004) |
| [39••] (2010) | Various | 343 (~54) | ~39 (11) | Setting: hospital/medical health clinic; method: SSADDA, includes PTSD, interview; time from E: “lifetime” | 2084 (~54) | ~39 (11) | NSF | Yes | Yes | United States/NHW; United States/AA | FKBP5; rs3800373, rs9296158, rs1360780, rs9470080 | rs3800373, rs9296158, and rs9470080 associated with PTSD in AA only (P<0.05); AA with rs9470080 T/T had the lowest risk of PTSD compared with other genotypes in the absence of childhood adversity exposure but had the highest risk when exposed (P=0.008 for interaction); NHW rs3800373 (risk A), rs9296158 (G), rs1360780 (C), and rs9470080 (C) carriers had higher risk of PTSD if they were also alcohol dependent compared with those with other genotypes (P for interaction, NR) |
| [33] (2005) | Combat | 118 (100) | 56 (4) | Setting: PTSD clinic; method: SI: CAPS, DSM-IV; time from E: NR | 42 (100) | 61 (7) | Yes | No | No | Australia/NHW | GCCR; rs6189, rs6190, rs56149945 | No significant association between GCCR SNPs and PTSD |
| [40] (2008) | Not specified | Child: 6 (67); parents: 25 (24) 17 (29) |
NR | Setting: ADHD genetic study; method: SSI: KSADS-PL (child), SADS-LAR (adult); time from E: NR (“lifetime”) Setting: cohort; method: SADS-LAR?; time from E: NR (“lifetime”) |
Child: 181 (70); parent: 291 (52) 292 (67) |
NR | NSF – |
Yes – |
Yes – |
United States/NHW Finland/NHW |
CNR1; rs806369, rs1049353, rs806377, rs6454674 rs806369, rs1049353, rs806377, rs6454674 |
rs1049353 A associated with PTSD in parents (P=0.011); haplotype (rs806369, rs1049353): excess C–A and C–G variants in parents of youth with ADHD who report PTSD No association with PTSD |
| [34] (2002) | Combat | 77 (100) | NR | Setting: VA clinic; method: SCID; time from E: NR | 202 (100) | NR | NSF | Yes | Yes | United States/NHW | NPY; rs16139 | No association between NPY SNP and PTSD |
| [37] (2007) | Combat | 133 (100) | 40 (7) | Setting: military unit; method: SCID, DSM-IV; time from E: “current” and “chronic” | 34 (100) | 38 (4) | Yes | No | No | Croatia/Caucasian | DBH; rs1611115 | No association between SNP and PTSD; SNP associated with DBH levels (P=0.0001) |
| [41] (2009) | Various | 46 (NR) | NR | Setting: adult twin study; method: telephone interview, DSM-IV; time from E: NR | 213 (NR) | NR | NSF | Yes | Yes | NR | GABRA2; rs279836, rs279826, rs279858, rs279871 | No main effect of gene/variant on PTSD risk; significant interaction (P<0.05) between composite lifetime history of trauma exposure and 3 of 4 risk alleles for adult PTSD |
| [42] (2010) | 1994 Rwandan genocide/war; TE: 36 war- and non–war- related types | 340 (~53) | ~35 | Setting: refugee during war; method: SI: PDS; time from E: 12–13 y (“lifetime” and “current”) | 84 (~53) | ~35 | Yes | No | No | Rwanda | COMT; rs4680 | No main effect of gene/variant on PTSD risk; significant interaction (P=0.04) between genotype and number of traumatic event types. Met/Met were at high risk for lifetime PTSD independent of number of traumatic events types, whereas Val/Val showed typical dose–response of traumatic event types and risk for PTSD |
| [36] (2006) | Various | 107 (42) | 34 (10) | Setting: hospital; method: SCID-Kor, DSM-IV; time from E: NR | 161 (32) | 32 (10) | NSF | Yes | Yes | Korea/Korean | BDNF; rs6265 | No association between BDNF SNP and PTSD |
| [35] (2006) | Various | 96 (76) | 44 (7) | Setting: VA clinic; method: SCID, SADS-L, DSM-III; time from E: NR | 250 (41) | 38 (20) | NSF | NR | No | United States/NHW | BDNF, G-712A, C270T; rs6265 | No association between BDNF SNPs and PTSD |
| [43] (2005) | Combat | 54 (100) | 53 (6) | Setting: PTSD treatment program; method: CAPS-2, SCID, DSM-IV; time from E: NR | – | – | – | Yes | – | United States/NHW | APOE | APOE ε2 allele associated with higher CAPS-2 re-experiencing scores (P=0.001) |
| [44] (2009) | Hurricane 2004 (Florida); various | 607 (35) | Adults | Setting: epidemiologic exposure; method: telephone interview, National Women’s Study PTSD module; time from E: 6 mo (“current” and “lifetime”) | – | – | – | Yes | – | United States/NHW; United States/AA, HW, As | RGS2; rs4606 | Significant 3-way interaction for posthurricane PTSD symptoms (P=0.03) and lifetime PTSD symptoms (P<0.001); “C” allele increased risk under high environmental stress conditions (high hurricane exposure/PTE and low social support) |
AA African American, ADHD attention-deficit/hyperactivity disorder, As Asian, CAPS Clinician Administered Posttraumatic Stress Disorder Scale, dbSNP Single Nucleotide Polymorphism Database, E trauma exposure, HW Hispanic white, KSADS-PL Kids’ Schedule for Affective Disorders and Schizophrenia-Present and Lifetime, MD major depression, MINI Mini International Neuropsychiatric Interview, NHW non-Hispanic white, NR not reported, NSF not selected for, PDEQ Peritraumatic Dissociative Experiences Questionnaire, PDI Peritraumatic Distress Inventory, PDS Posttraumatic Diagnostic Scale, PSS Posttraumatic Stress Disorder Symptom Scale, PTE post-traumatic event, PTSD post-traumatic stress disorder, PTSD-C Post-Traumatic Stress Disorder Clinical Questionnaire, PTSD-F Post-Traumatic Stress Disorder Factor Questionnaire, SADS-L Schedule for Affective Disorders and Schizophrenia-Lifetime, SADS-LAR Schedule for Affective Disorders and Schizophrenia, SCID Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, SCID-Kor SCID, Korean version, SI structured interview, SNP single nucleotide polymorphism, SSADDA Semi-Structured Assessment for Drug Dependence and Alcoholism, SSI semistructured interview, TE traumatic event, UTR untranslated region, VA Veterans Affairs, VNTR variable number of tandem repeats