Association of HLA locus alleles with posttraumatic stress disorder

Katrinli, Şeyma; Lori, Adriana; Kilaru, Varun; Carter, Sierra; Powers, Abigail; Gillespie, Charles F.; Wingo, Aliza P.; Michopoulos, Vasiliki; Jovanović, Tanja; Ressler, Kerry J.; Smith, Alicia K.

doi:10.1016/j.bbi.2019.07.016

Cited by 30 publications

(29 citation statements)

References 31 publications

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“…WGCNA have been widely used in various medical fields, such as tumor ( Xiang Z. et al, 2019 ), neurological and psychiatric disorders ( Katrinli et al, 2019 ; Tang and Liu, 2019 ), chronic disease ( Chen et al, 2019 ), and infectious diseases ( Bando et al, 2019 ). What’s more, most of the conclusions drawn from WGCNA can be further confirmed by bioinformatics analyses or biological experiments, which guarantees the high reliability of WGCNA.…”

Section: Introductionmentioning

confidence: 99%

Identification of KIF18B as a Hub Candidate Gene in the Metastasis of Clear Cell Renal Cell Carcinoma by Weighted Gene Co-expression Network Analysis

et al. 2020

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Background: Clear cell renal cell carcinoma (ccRCC) is a common type of fatal malignancy in the urinary system. As the therapeutic strategies of ccRCC are severely limited at present, the prognosis of patients with metastatic carcinoma is usually not promising. Revealing the pathogenesis and identifying hub candidate genes for prognosis prediction and precise treatment are urgently needed in metastatic ccRCC. Methods: In the present study, we conducted a series of bioinformatics studies with the gene expression profiles of ccRCC samples from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) database for identifying and validating the hub gene of metastatic ccRCC. We constructed a co-expression network, divided genes into co-expression modules, and identified ccRCC-related modules by weighted gene co-expression network analysis (WGCNA) with data from GEO. Then, we investigated the functions of genes in the ccRCC-related modules by enrichment analyses and built a sub-network accordingly. A hub candidate gene of the metastatic ccRCC was identified by maximal clique centrality (MCC) method. We validate the hub gene by differentially expressed gene analysis, overall survival analysis, and correlation analysis with clinical traits with the external dataset (TCGA). Finally, we explored the function of the hub gene by correlation analysis with targets of precise therapies and single-gene gene set enrichment analysis. Results: We conducted WGCNA with the expression profiles of GSE73731 from GEO and divided all genes into 8 meaningful co-expression modules. One module is proved to be positively correlated with pathological stage and tumor grade of ccRCC. Genes in the ccRCC-related module were mainly enriched in functions of mitotic cell division and several proverbial tumor related signal pathways. We then identified KIF18B as a hub gene of the metastasis of ccRCC. Validating analyses in external dataset observed the up-regulation of KIF18B in ccRCC and its correlation with worse outcomes. Further analyses found that the expression of KIF18B is related to that of targets of precise therapies.

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Section: Introductionmentioning

confidence: 99%

Identification of KIF18B as a Hub Candidate Gene in the Metastasis of Clear Cell Renal Cell Carcinoma by Weighted Gene Co-expression Network Analysis

et al. 2020

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“…Furthermore, whereas the PRISMO study is entirely based on subjects of European ancestry, the US MRS and Army STARRS studies include more ancestral diversity. Genes in the HLA region tend to be highly polymorphic, particularly with respect to ancestral background [48]. Thus, it is possible that this heterogeneity may contribute to the lack of replication.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal epigenome-wide association studies of three male military cohorts reveal multiple CpG sites associated with post-traumatic stress disorder

et al. 2020

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Background: Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 traumaexposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a twostage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a metaanalysis. Results: Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, postdeployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 × 10 −08) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region.

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“…Analysis of HLA-DRB5 gene expression in peripheral blood might serve as a remission predictor for antidepressant treatment in late-life depression [ 201 ]. In addition, an association between HLA-DRB1 and post-traumatic stress disorder has been reported [ 202 ]. It can also be used as predictor of brain and cerebellar atrophy in patients with Gulf War Illness (GWI), a disease of veterans of the 1991 Gulf War [ 203 ].…”

Section: Dcs In Mood Disorders and Depression-like Behaviormentioning

confidence: 99%

Dendritic Cells: Neglected Modulators of Peripheral Immune Responses and Neuroinflammation in Mood Disorders?

Dantas

Freff

Ambrée

et al. 2021

Cells

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Affective disorders (AD) including major depressive disorder (MDD) and bipolar disorder (BD) are common mood disorders associated with increased disability and poor health outcomes. Altered immune responses characterized by increased serum levels of pro-inflammatory cytokines and neuroinflammation are common findings in patients with AD and in corresponding animal models. Dendritic cells (DCs) represent a heterogeneous population of myeloid cells that orchestrate innate and adaptive immune responses and self-tolerance. Upon sensing exogenous and endogenous danger signals, mature DCs secrete proinflammatory factors, acquire migratory and antigen presenting capacities and thus contribute to neuroinflammation in trauma, autoimmunity, and neurodegenerative diseases. However, little is known about the involvement of DCs in the pathogenesis of AD. In this review, we summarize the current knowledge on DCs in peripheral immune responses and neuroinflammation in MDD and BD. In addition, we consider the impact of DCs on neuroinflammation and behavior in animal models of AD. Finally, we will discuss therapeutic perspectives targeting DCs and their effector molecules in mood disorders.

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Association of HLA locus alleles with posttraumatic stress disorder

Cited by 30 publications

References 31 publications

Identification of KIF18B as a Hub Candidate Gene in the Metastasis of Clear Cell Renal Cell Carcinoma by Weighted Gene Co-expression Network Analysis

Identification of KIF18B as a Hub Candidate Gene in the Metastasis of Clear Cell Renal Cell Carcinoma by Weighted Gene Co-expression Network Analysis

Longitudinal epigenome-wide association studies of three male military cohorts reveal multiple CpG sites associated with post-traumatic stress disorder

Dendritic Cells: Neglected Modulators of Peripheral Immune Responses and Neuroinflammation in Mood Disorders?

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