Genetic Association Analysis of 300 Genes Identifies a Risk Haplotype in SLC18A2 for Post-traumatic Stress Disorder in Two Independent Samples

The genetic architecture of post-traumatic stress disorder (PTSD) remains poorly understood with the vast majority of genetic association studies reporting on single candidate genes. We conducted a large genetic study in trauma-exposed European-American women (N=2538; 845 PTSD cases, 1693 controls)...

Full description

Saved in:
Bibliographic Details
Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2014-07, Vol.39 (8), p.1872-1879
Main Authors: SOLOVIEFF, Nadia, ROBERTS, Andrea L, GALEA, Sandro, SMOLLER, Jordan W, PURCELL, Shaun M, KOENEN, Karestan C, RATANATHARATHORN, Andrew, HALOOSIM, Michelle, DE VIVO, Immaculata, KING, Anthony P, LIBERZON, Israel, AIELLO, Allison, UDDIN, Monica, WILDMAN, Derek E
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Anxiety disorders. Neuroses
Biological and medical sciences
Biomarkers
Epidemiology
Female
Genes
Genetic Association Studies
Genetic Predisposition to Disease
Genomes
Genomics
Haplotypes
Humans
Independent sample
Medical sciences
Medicine
Middle Aged
Neurosciences
Original
Polymorphism, Single Nucleotide
Post traumatic stress disorder
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Public health
Risk Factors
Stress Disorders, Post-Traumatic - genetics
Trauma
Vesicular Monoamine Transport Proteins - genetics
Women
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The genetic architecture of post-traumatic stress disorder (PTSD) remains poorly understood with the vast majority of genetic association studies reporting on single candidate genes. We conducted a large genetic study in trauma-exposed European-American women (N=2538; 845 PTSD cases, 1693 controls) by testing 3742 SNPs across more than 300 genes and conducting polygenic analyses using results from the Psychiatric Genome-Wide Association Studies Consortium (PGC). We tested the association between each SNP and two measures of PTSD, a severity score and diagnosis. We found a significant association between PTSD (diagnosis) and SNPs (top SNP: rs363276, odds ratio (OR)=1.4, p=2.1E-05) in SLC18A2 (vesicular monoamine transporter 2). A haplotype analysis of 9 SNPs in SLC18A2, including rs363276, identified a risk haplotype (CGGCGGAAG, p=0.0046), and the same risk haplotype was associated with PTSD in an independent cohort of trauma-exposed African-Americans (p=0.049; N=748, men and women). SLC18A2 is involved in transporting monoamines to synaptic vesicles and has been implicated in a number of neuropsychiatric disorders including major depression. Eight genes previously associated with PTSD had SNPs with nominally significant associations (p
ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2014.34