Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors

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dc.contributor.authorNothling, Janien_ZA
dc.contributor.authorAbrahams, Naeemahen_ZA
dc.contributor.authorToikumo, Sylvanusen_ZA
dc.contributor.authorSuderman, Matthewen_ZA
dc.contributor.authorMhlongo, Shibeen_ZA
dc.contributor.authorLombard, Carlen_ZA
dc.contributor.authorSeedat, Sorayaen_ZA
dc.contributor.authorHemmings, Sian Megan Joannaen_ZA
dc.date.accessioned2021-12-09T06:28:32Z
dc.date.available2021-12-09T06:28:32Z
dc.date.issued2019
dc.descriptionCITATION: Nothling, J., et al. 2021. Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors. Translational Psychiatry, 11:594, doi:10.1038/s41398-021-01608-z.
dc.descriptionThe original publication is available at https://www.nature.com
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractENGLISH ABSTRACT: Rape is associated with a high risk for posttraumatic stress disorder (PTSD). DNA methylation changes may confer risk or protection for PTSD following rape by regulating the expression of genes implicated in pathways affected by PTSD. We aimed to: (1) identify epigenome-wide differences in methylation profiles between rape-exposed women with and without PTSD at 3-months post-rape, in a demographically and ethnically similar group, drawn from a low-income setting; (2) validate and replicate the findings of the epigenome-wide analysis in selected genes (BRSK2 and ADCYAP1); and (3) investigate baseline and longitudinal changes in BRSK2 and ADCYAP1 methylation over six months in relation to change in PTSD symptom scores over 6 months, in the combined discovery/validation and replication samples (n = 96). Rape-exposed women (n = 852) were recruited from rape clinics in the Rape Impact Cohort Evaluation (RICE) umbrella study. Epigenome-wide differentially methylated CpG sites between rape-exposed women with (n = 24) and without (n = 24) PTSD at 3-months post-rape were investigated using the Illumina EPIC BeadChip in a discovery cohort (n = 48). Validation (n = 47) and replication (n = 49) of BRSK2 and ADCYAP1 methylation findings were investigated using EpiTYPER technology. Longitudinal change in BRSK2 and ADCYAP1 was also investigated using EpiTYPER technology in the combined sample (n = 96). In the discovery sample, after adjustment for multiple comparisons, one differentially methylated CpG site (chr10: 61385771/ cg01700569, p = 0.049) and thirty-four differentially methylated regions were associated with PTSD status at 3-months post-rape. Decreased BRSK2 and ADCYAP1 methylation at 3-months and 6-months post-rape were associated with increased PTSD scores at the same time points, but these findings did not remain significant in adjusted models. In conclusion, decreased methylation of BRSK2 may result in abnormal neuronal polarization, synaptic development, vesicle formation, and disrupted neurotransmission in individuals with PTSD. PTSD symptoms may also be mediated by differential methylation of the ADCYAP1 gene which is involved in stress regulation. Replication of these findings is required to determine whether ADCYAP1 and BRSK2 are biomarkers of PTSD and potential therapeutic targets.en_ZA
dc.description.urihttps://www.nature.com/articles/s41398-021-01608-z
dc.description.versionPublisher's version
dc.format.extent21 pagesen_ZA
dc.identifier.citationNothling, J., et al. 2021. Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors. Translational Psychiatry, 11:594, doi:10.1038/s41398-021-01608-z
dc.identifier.issn2158-3188 (online)
dc.identifier.otherdoi:10.1038/s41398-021-01608-z
dc.identifier.urihttp://hdl.handle.net/10019.1/123542
dc.language.isoen_ZAen_ZA
dc.publisherSpringer Natureen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectPosttraumatic stress disorderen_ZA
dc.subjectDNA -- Methylationen_ZA
dc.subjectPost-rape traumaen_ZA
dc.subjectSexual assault trauma syndromeen_ZA
dc.titleGenome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivorsen_ZA
dc.typeArticleen_ZA
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