Table 1 Summary of epigenome-wide association studies investigating posttraumatic stress disorder as the outcome.
Reference | Array and tissue type | Design and sample size | Setting and trauma type | Ethnicity | Gender and mean age | PTSD measure | PTSD associated genes/networks |
|---|---|---|---|---|---|---|---|
Uddin et al. [18] | HM27; Blood | Cross-sectional; 23 PTSD cases 77 trauma-exposed controls | Civilians from the DNHS cohort; mixture of trauma types | 79 African American, 14 Caucasian, 7 other ethnicities (not specified) | 40 Male (40%) 60 (60%) Female; 45.8 years | PCL-C | Functional annotation clustering of differentially methylated genes implicated genes associated with the immune system in the development of PTSD. |
Smith et al. [13] | HM27; Blood | Cross-sectional; 51 PTSD cases 53 trauma-exposed controls | Civilians from the GTP cohort; mixture of trauma types | 104 African American | 64 Male (61.5%) 40 Female (38.5%); 42.7 years | CAPS | Epigenome-wide significant differences in methylation at CpG sites in the APC5, TLR8, TPR, CLEC9A, ANXA2 genes. |
Mehta et al. [11] | 450 K; Blood | Cross-sectional; 32 PTSD cases with CT 29 PTSD cases without CT | Civilian; mixture of trauma types | 150 African Americans, 19 other ethnicities | 18 Male (29.5%), 43 Female (70.5%); 41.6 years | PSS | Pathways affected by PTSD were related to apoptosis and cellular growth rate. Pathways uniquely affected in those with PTSD and CT were related to nervous system development and tolerance induction. |
Chen, Kobayasji and Mellman, 2016 [19] | 450 K; Blood | Cross-sectional; 12 PTSD cases 12 trauma-exposed controls | Civilian; index traumas: 8 childhood physical or sexual abuse (33.3%); 3 sexual assault (12.5%); 9 violent crime (37.5%); 2 IPV (8.3%); 2 witnessed a violent death (8.3%) | 24 African American | 13 Male (54.2%) 11 Female (45.8%); 22 years | CAPS | No epigenome-wide significant differences in methylation levels. Expression of genes associated with olfactory receptors, immune activation, GABAA receptor, and vitamin D synthesis was upregulated in PTSD cases. |
Hammamieh et al. 2017 [12] | 450 K; Blood | Cross-sectional; 79 PTSD cases 80 trauma-exposed controls | Combat exposed veterans previously deployed to Iraq or Afghanistan | 159 American ethnically matched participants (not otherwise specified) | 159 Males (100%); 33.9 years | CAPS | Functional enrichment analysis of differentially methylated genes implicated genes related to nervous system development/functioning, somatic complications, and endocrine signaling in the development of PTSD. |
Kuan et al. 2017 [20] | 450 K; Blood | Cross-sectional; 171 current PTSD cases 100 past PTSD cases 202 trauma-exposed controls | Civilian responders to the September 11th World Trade Centre Disaster from the WTC cohort | 382 Caucasian Americans, 91 other ethnicities (not specified) | 473 Males (100%); 49.5 years | SCID | No epigenome-wide significant differences in methylation levels. Differential methylation at CpG sites in the ZDHHC11, CSMD2, COL9A3, PDCD6IP, TBC1D24, and FAM164A genes were associated with current PTSD at a nominal level. |
Mehta et al. [14] | EPIC; Blood | Cross-sectional; 8 PTSD cases 48 trauma-exposed controls | Treatment seeking Vietnam veterans with combat exposure | 96 Australian (not otherwise specified) | 96 Males (100%); 68.67 years | CAPS | Epigenome-wide significant differences in methylation at CpG sites in the BRSK1, NGF, LCN8, DOCK2 genes and at an intergenic site (closest gene LRRC3B). |
Kryzewska et al. [24] | 450 K, Blood | Cross-sectional;v34 PTSD cases 39 trauma-exposed controls | Police officers | 73 Dutch | 38 (52.1%) Males, 35 (47.9%) Females | CAPS | No epigenome-wide significant differences in methylation levels. |
Maddox et al. [17] | 450 K; Blood | Cross-sectional; 109 PTSD cases, 169 trauma-exposed controls | Civilians from the GTP cohort; mixture of trauma types | 278 predominately African American | 278 (100%) Females | PSS | Genome-wide significant difference in methylation at one CpG site in HDAC4. |
Rutten et al. [15] | 450 K; Blood | Discovery dataset: longitudinal; 32 high PTSD, high trauma 29 low PTSD, high trauma 32 low PTSD, low trauma Replication dataset: longitudinal; 35 cases with PTSD 63 trauma exposure controls | Military soldiers with combat exposure, pre-deployment and post-deployment (minimum of 4 months) to Afghanistan from the PRISMO cohort. Marines with combat exposure, pre-deployment and post-deployment to Iraq or Afghanistan from the MRS cohort | 93 Dutch Caucasian soldiers and 98 North American marines | 93 Males (100%); 27.5 years and 98 Males (100%); 22 years | SRIP or CAPS | Longitudinal changes in PTSD symptoms were associated with differential methylation at CpG sites in the DUSP22, NINJ2, HOOK2, SDK1, MYT1L, PAX8, COL1A2, and HIST1H2APS2 genes in the PRISMO cohort. The finding related to HIST1H2APS2 was replicated in the MRS cohort. |
Uddin et al. [21] | 450 K, Blood | Cross-sectional, meta-analysis; 198 with PTSD 347 trauma-exposed controls | Civilians from the DNHS, GTP, and WTC cohorts; mixture of trauma types | 343 African American, 164 Caucasian American, 38 other ethnicities (not specified) | 294 Males (54%), 251 Females (46%), 46.6 years | PCL-C CAPS SCID | Epigenome-wide significant differences in methylation of CpG sites in the NRG1 and HGS genes. |
Logue et al. [25] | EPIC, Blood | Cross-sectional; 378 PTSD cases 135 trauma-exposed controls | War veterans exposed to combat trauma in Iraq and/or Afghanistan form the TRACTS cohorts and veterans recruited from TBI-VA-Boston | 513 American veterans (not otherwise specified) | 467 (91%) Males, 46 (9%) Females, 32.7 years | CAPS | Epigenome-wide significant difference in methylation of a CpG site in the G0S2 gene. |
Snijders et al. [16] | 450 K; Blood | Longitudinal; 123 PTSD cases 143 trauma-exposed controls | Military (marine and army) combat exposed personnel from the MRS, STARRS, and PRISMO cohorts, deployed to Iraq or Afghanistan for 4 to 7 months | 126 predominately Caucasian American marines, 78 Caucasian American army soldiers, 62 Dutch army soldiers | 266 (100%) Males; 24.5 years | CAPS, PCL/CIDI-SC and SRIP | Epigenome-wide significant differences in methylation of CpG sites in the SPRY4, SDK1, CTRC, CDH15, MAD1L1, HEXDC genes. |
Smith et al. [22] | 450 K, Blood | Cross-sectional, meta-analysis; 878 PTSD cases 1018 trauma-exposed controls | Three civilian samples and seven combat samples all exposed to trauma including combat and various civilian traumas from the DNHS, GTP, WTC, STARRS, MRS, INTRusST, PRISMO, VA-M-EA, VA-M-AA, and VA-NCPTSD cohorts | 986 Caucasian American, 62 Dutch, 777 African American, 57 Hispanic, 76 other ethnicities (not specified) | 1303 (68.7%) Males, 593 (31.3%) Females, 35.8 years | PCL-C, DSM-IV, CAPS, MINI, SCID, CIDI-SC, SRIP | Epigenome-wide significant differences in methylation of CpG sites in the AHRR, RNF6, MIR3170, ATP9A, AC011899.9, FLJ46321, and LINC00599 genes. |
