Association of HLA locus alleles with posttraumatic stress disorder.

Brain Behav Immun 2019 Oct 13;81:655-658. Epub 2019 Jul 13.

Emory University, Department of Gynecology and Obstetrics, Atlanta, GA, USA; Emory University, Department of Psychiatry & Behavioral Sciences, Atlanta, GA, USA. Electronic address:

Background: Immune dysregulation has been widely observed in those with posttraumatic stress disorder (PTSD). An individual's immune response is shaped, in part, by the highly polymorphic Human Leukocyte Antigen (HLA) locus that is associated with major psychiatric disorders such as schizophrenia, major depression and bipolar disorder. The aim of the current study was to investigate the association between common HLA alleles and PTSD.

Methods: Genome-wide association data was used to predict alleles of 7 classical polymorphic HLA genes (A, B, C, DRB1, DQA1, DQB1, DPB1) in 403 lifetime PTSD cases and 369 trauma exposed controls of African ancestry. Association of HLA allelic variations with lifetime PTSD was analyzed using logistic regression, controlling for ancestry, sex and multiple comparisons. The effect of HLA alleles on gene expression was assessed by weighted correlation network analysis (WGCNA), using 353 subjects with available expression data. Enrichment analysis was performed using anRichment to identify associated pathways of each module.

Results: HLA-B*58:01 (p = 0.035), HLA-C*07:01 (p = 0.035), HLA-DQA1*01:01 (p = 0.003), HLA-DQB1*05:01 (p = 0.009) and HLA-DPB1*17:01 (p = 0.017) were more common in PTSD cases, while HLA-A*02:01 (p = 0.026), HLA-DQA1*05:05 (p = 0.011) and HLA-DRB1*11:01 (p < 0.001) were more frequent in controls. WGCNA was used to explore expression patterns of the PTSD related alleles. Gene expression modules of PTSD-related HLA alleles were enriched in various pathways, including pathways related to immune and neural activity.

Conclusions: To the best of our knowledge, this is the first study to report an association of HLA alleles with PTSD. Altogether, our results support the link between the immune system, brain and PTSD.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S08891591193017
Publisher Site
http://dx.doi.org/10.1016/j.bbi.2019.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754776PMC
October 2019
4 Reads

Publication Analysis

Top Keywords

stress disorder
8
lifetime ptsd
8
ptsd cases
8
hla alleles
8
posttraumatic stress
8
association hla
8
hla locus
8
hla
5
hla genes
4
alleles classical
4
hla-dqa1*0101 p = 0003
4
predict alleles
4
classical polymorphic
4
polymorphic hla
4
sex multiple
4
data predict
4
genes drb1
4
p = 0035 hla-dqa1*0101
4
performed anrichment
4
genome-wide association
4

Altmetric Statistics

Similar Publications