Premium
Genetic risk mechanisms of posttraumatic stress disorder in the human brain
Author(s) -
Bharadwaj Rahul A.,
Jaffe Andrew E.,
Chen Qiang,
DeepSoboslay Amy,
Goldman Aaron L.,
Mighdoll Michelle I.,
Cotoia John A.,
Brandtjen Anna C.,
Shin JooHeon,
Hyde Thomas M.,
Mattay Venkata S.,
Weinberger Daniel R.,
Kleinman Joel E.
Publication year - 2018
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23957
Subject(s) - expression quantitative trait loci , dorsolateral prefrontal cortex , quantitative trait locus , snp , genotype , exon , genetics , prefrontal cortex , gene , biology , amygdala , genetic association , genome wide association study , allele , psychology , single nucleotide polymorphism , neuroscience , cognition
Posttraumatic stress disorder (PTSD) follows exposure to a traumatic event in susceptible individuals. Recently, genome‐wide association studies have identified a number of genetic sequence variants that are associated with the risk of developing PTSD. To follow up on identifying the molecular mechanisms of these risk variants, we performed genotype to RNA sequencing–derived quantitative expression (whole gene, exon, and exon junction levels) analysis in the dorsolateral prefrontal cortex (DLPFC) of normal postmortem human brains. We further investigated genotype–gene expression associations within the amygdala in a smaller independent RNA sequencing (Genotype‐Tissue Expression [GTEx]) dataset. Our DLPFC analyses identified significant expression quantitative trait loci (eQTL) associations for a “candidate” PTSD risk SNP rs363276 and the expression of two genes: SLC18A2 and PDZD8 , where the PTSD risk/minor allele T was associated with significantly lower levels of gene expression for both genes, in the DLPFC. These eQTL associations were independently confirmed in the amygdala from the GTEx database. Rs363276 “T” carriers also showed significantly increased activity in the amygdala during an emotional face‐matching task in healthy volunteers. Taken together, our preliminary findings in normal human brains represent a tractable approach to identify mechanisms by which genetic variants potentially increase an individual's risk for developing PTSD. © 2016 Wiley Periodicals, Inc.