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

AbstractThe 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 m ethodological 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 marker s 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 inFKBP5 and rs258747 inNR3C1) were nominally associated with PTSD,ps = .001 and .001, respectively, following multiple testing correction. At the gene level, significant relations between PTSD and bothNR3C1 andFKBP5 were detected and robust to sensitivity analyses. Although study limitations exist (e.g., varied outcomes, ina...
Source: Journal of Traumatic Stress - Category: Psychiatry & Psychology Authors: Tags: Research Article Source Type: research