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Neuropsychopharmacology DOI:10.1038/npp.2014.34

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

Publication TypeJournal Article
Year of Publication2014
AuthorsSolovieff, N, Roberts, AL, Ratanatharathorn, A, Haloosim, M, De Vivo, I, King, AP, Liberzon, I, Aiello, A, Uddin, M, Wildman, DE, Galea, S, Smoller, JW, Purcell, SM, Koenen, KC
JournalNeuropsychopharmacology
Volume39
Issue8
Pages1872-9
Date Published2014 Jul
ISSN1740-634X
KeywordsFemale, Genetic Association Studies, Genetic Predisposition to Disease, Haplotypes, Humans, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Stress Disorders, Post-Traumatic, Vesicular Monoamine Transport Proteins
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

URLhttp://dx.doi.org/10.1038/npp.2014.34
DOI10.1038/npp.2014.34
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24525708?dopt=Abstract

Alternate JournalNeuropsychopharmacology
PubMed ID24525708
PubMed Central IDPMC4059895
Grant ListRC4MH092707 / 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