Home > Research > Publications & Outputs > Integrated genetic, epigenetic, and gene set en...

Research

Links

Text available via DOI:

Keywords

View graph of relations

Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts. / Conrad, Daniela; Wilker, Sarah; Schneider, Anna et al.
In: Psychophysiology, Vol. 57, No. 1, e13288, 01.01.2020.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Conrad, D, Wilker, S, Schneider, A, Karabatsiakis, A, Pfeiffer, A, Kolassa, S, Freytag, V, Vukojevic, V, Vogler, C, Milnik, A, Papassotiropoulos, A, J.-F. de Quervain, D, Elbert, T & Kolassa, IT 2020, 'Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts', Psychophysiology, vol. 57, no. 1, e13288. https://doi.org/10.1111/psyp.13288

APA

Conrad, D., Wilker, S., Schneider, A., Karabatsiakis, A., Pfeiffer, A., Kolassa, S., Freytag, V., Vukojevic, V., Vogler, C., Milnik, A., Papassotiropoulos, A., J.-F. de Quervain, D., Elbert, T., & Kolassa, I. T. (2020). Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts. Psychophysiology, 57(1), Article e13288. https://doi.org/10.1111/psyp.13288

Vancouver

Conrad D, Wilker S, Schneider A, Karabatsiakis A, Pfeiffer A, Kolassa S et al. Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts. Psychophysiology. 2020 Jan 1;57(1):e13288. doi: 10.1111/psyp.13288

Author

Conrad, Daniela ; Wilker, Sarah ; Schneider, Anna et al. / Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma : Results from two independent African cohorts. In: Psychophysiology. 2020 ; Vol. 57, No. 1.

Bibtex

@article{371f419f8fce4d6c948d34ebd619830d,
title = "Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma: Results from two independent African cohorts",
abstract = "The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1–4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell–cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1–4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N1 = 924) and Rwanda (N2 = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (puncorrected= 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (puncorrected= 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (pcorrected= 0.003) and NOTCH receptor processing (pcorrected= 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.",
keywords = "candidate gene analysis, epigenetics, gene set enrichment analysis, MAGMA, NOTCH, posttraumatic stress disorder",
author = "Daniela Conrad and Sarah Wilker and Anna Schneider and Alexander Karabatsiakis and Anett Pfeiffer and Stephan Kolassa and Virginie Freytag and Vanja Vukojevic and Christian Vogler and Annette Milnik and Andreas Papassotiropoulos and {J.-F. de Quervain}, Dominique and Thomas Elbert and Kolassa, {Iris Tatjana}",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/psyp.13288",
language = "English",
volume = "57",
journal = "Psychophysiology",
issn = "0048-5772",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "1",

}

RIS

TY - JOUR

T1 - Integrated genetic, epigenetic, and gene set enrichment analyses identify NOTCH as a potential mediator for PTSD risk after trauma

T2 - Results from two independent African cohorts

AU - Conrad, Daniela

AU - Wilker, Sarah

AU - Schneider, Anna

AU - Karabatsiakis, Alexander

AU - Pfeiffer, Anett

AU - Kolassa, Stephan

AU - Freytag, Virginie

AU - Vukojevic, Vanja

AU - Vogler, Christian

AU - Milnik, Annette

AU - Papassotiropoulos, Andreas

AU - J.-F. de Quervain, Dominique

AU - Elbert, Thomas

AU - Kolassa, Iris Tatjana

PY - 2020/1/1

Y1 - 2020/1/1

N2 - The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1–4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell–cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1–4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N1 = 924) and Rwanda (N2 = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (puncorrected= 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (puncorrected= 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (pcorrected= 0.003) and NOTCH receptor processing (pcorrected= 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.

AB - The risk of developing posttraumatic stress disorder (PTSD) increases with the number of traumatic event types experienced (trauma load) in interaction with other psychobiological risk factors. The NOTCH (neurogenic locus notch homolog proteins) signaling pathway, consisting of four different trans-membrane receptor proteins (NOTCH1–4), constitutes an evolutionarily well-conserved intercellular communication pathway (involved, e.g., in cell–cell interaction, inflammatory signaling, and learning processes). Its association with fear memory consolidation makes it an interesting candidate for PTSD research. We tested for significant associations of common genetic variants of NOTCH1–4 (investigated by microarray) and genomic methylation of saliva-derived DNA with lifetime PTSD risk in independent cohorts from Northern Uganda (N1 = 924) and Rwanda (N2 = 371), and investigated whether NOTCH-related gene sets were enriched for associations with lifetime PTSD risk. We found associations of lifetime PTSD risk with single nucleotide polymorphism (SNP) rs2074621 (NOTCH3) (puncorrected= 0.04) in both cohorts, and with methylation of CpG site cg17519949 (NOTCH3) (puncorrected= 0.05) in Rwandans. Yet, none of the (epi-)genetic associations survived multiple testing correction. Gene set enrichment analyses revealed enrichment for associations of two NOTCH pathways with lifetime PTSD risk in Ugandans: NOTCH binding (pcorrected= 0.003) and NOTCH receptor processing (pcorrected= 0.01). The environmental factor trauma load was significant in all analyses (all p < 0.001). Our integrated methodological approach suggests NOTCH as a possible mediator of PTSD risk after trauma. The results require replication, and the precise underlying pathophysiological mechanisms should be illuminated in future studies.

KW - candidate gene analysis

KW - epigenetics

KW - gene set enrichment analysis

KW - MAGMA

KW - NOTCH

KW - posttraumatic stress disorder

U2 - 10.1111/psyp.13288

DO - 10.1111/psyp.13288

M3 - Journal article

C2 - 30328613

AN - SCOPUS:85055152251

VL - 57

JO - Psychophysiology

JF - Psychophysiology

SN - 0048-5772

IS - 1

M1 - e13288

ER -