Genetic association analysis of 300 genes identifies a risk haplotype in SLC18A2 for post-traumatic stress disorder in two independent samples.

Neuropsychopharmacology
Authors
Keywords
Abstract

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

Year of Publication
2014
Journal
Neuropsychopharmacology
Volume
39
Issue
8
Pages
1872-9
Date Published
2014 Jul
ISSN
1740-634X
URL
DOI
10.1038/npp.2014.34
PubMed ID
24525708
PubMed Central ID
PMC4059895
Links
Grant list
RC4MH092707 / MH / NIMH NIH HHS / United States
R01 DA022720 / DA / NIDA NIH HHS / United States
R01 MH093612 / MH / NIMH NIH HHS / United States
RC1 MH088283 / MH / NIMH NIH HHS / United States
DA 022720-S1 / DA / NIDA NIH HHS / United States
P51 RR000165 / RR / NCRR NIH HHS / United States
RC4 MH092707 / MH / NIMH NIH HHS / United States
MH078928 / MH / NIMH NIH HHS / United States
R01 MH078928 / MH / NIMH NIH HHS / United States
MH088283 / MH / NIMH NIH HHS / United States
P51RR000165 / RR / NCRR NIH HHS / United States
DA022720 / DA / NIDA NIH HHS / United States