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

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...

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Autores principales:	Jani Nöthling, Naeemah Abrahams, Sylvanus Toikumo, Matthew Suderman, Shibe Mhlongo, Carl Lombard, Soraya Seedat, Sian Megan Joanna Hemmings
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/033b8a2e06674aee894fec8fa4813892
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spelling	oai:doaj.org-article:033b8a2e06674aee894fec8fa48138922021-11-21T12:07:47ZGenome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors10.1038/s41398-021-01608-z2158-3188https://doaj.org/article/033b8a2e06674aee894fec8fa48138922021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01608-zhttps://doaj.org/toc/2158-3188Abstract 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.Jani NöthlingNaeemah AbrahamsSylvanus ToikumoMatthew SudermanShibe MhlongoCarl LombardSoraya SeedatSian Megan Joanna HemmingsNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jani Nöthling Naeemah Abrahams Sylvanus Toikumo Matthew Suderman Shibe Mhlongo Carl Lombard Soraya Seedat Sian Megan Joanna Hemmings Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
description	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.
format	article
author	Jani Nöthling Naeemah Abrahams Sylvanus Toikumo Matthew Suderman Shibe Mhlongo Carl Lombard Soraya Seedat Sian Megan Joanna Hemmings
author_facet	Jani Nöthling Naeemah Abrahams Sylvanus Toikumo Matthew Suderman Shibe Mhlongo Carl Lombard Soraya Seedat Sian Megan Joanna Hemmings
author_sort	Jani Nöthling
title	Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
title_short	Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
title_full	Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
title_fullStr	Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
title_full_unstemmed	Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
title_sort	genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/033b8a2e06674aee894fec8fa4813892
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Genome-wide differentially methylated genes associated with posttraumatic stress disorder and longitudinal change in methylation in rape survivors

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