Mar 28, 2020

Meta-analysis of Associations Between Hypothalamic-Pituitary-Adrenal Axis Genes and Risk of Posttraumatic Stress Disorder

Journal of Traumatic Stress
Christina M SheerinNicole R Nugent


The hypothalamic-pituitary-adrenal (HPA) axis has been of interest in attempts to identify genetic vulnerability for posttraumatic stress disorder (PTSD). Although numerous HPA-axis genes have been implicated in candidate gene studies, the findings are mixed and interpretation is limited by study design and methodological inconsistencies. To address these inconsistencies in the PTSD candidate gene literature, we conducted meta-analyses of HPA-related genes from both a traditional single nucleotide polymorphism (SNP)-level analysis and a gene-level analysis, using novel methods aggregating markers in the same gene. Database searches (PubMed and PsycINFO) identified 24 unique articles examining six HPA-axis genes in PTSD; analyses were conducted on four genes (ADCYAP1R1, CRHR1, FKBP5, NR3C1) that met study eligibility criteria (original research, human subjects, main effect association study of selected genes, PTSD as an outcome, trauma-exposed control group) and had sufficient data and number of studies for use in meta-analysis, within 20 unique articles. Findings from SNP-level analyses indicated that two variants (rs9296158 in FKBP5 and rs258747 in NR3C1) were nominally associated with PTSD, ps = .001 and .001, respectively, f...Continue Reading

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Mentioned in this Paper

Hypothalamic Structure
Hypothalamic-pituitary-adrenal Axis
Gene Expression Analysis
Meta Analysis (Statistical Procedure)
Candidate Disease Gene

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