An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress.
An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress.
复制标题
对 PTSD 基因表达的分析表明，基因涉及糖皮质激素受体途径和应激神经反应。
DOI：
10.1016/j.psyneuen.2015.03.016
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发表时间：
2015
影响因子：
3.7
通讯作者：
Galea
中科院分区：
文献类型：
--
作者：
Logue,MarkW;Smith,AliciaK;Baldwin,Clinton;Wolf,ErikaJ;Guffanti,Guia;Ratanatharathorn,Andrew;Stone,Annjanette;Schichman,StevenA;Humphries,Donald;Binder,ElisabethB;Arloth,Janine;Menke,Andreas;Uddin,Monica;Wildman,Derek;Galea
我们研究了创伤后应激障碍（PTSD）和基因表达之间的关联，使用来自一组创伤暴露的白色非西班牙裔男性退伍军人（115例和28例对照）的全血样本。分析了10，264个基因和基因转录物的探针。我们发现41个基因在PTSD病例组和对照组中差异表达（多重检验校正p < 0.05）。最重要的是DSCAM，这是一种在发育中的大脑以及成年大脑的杏仁核和海马体中广泛表达的神经基因。然后，我们在使用两个重复队列的荟萃分析中检查了41个差异表达的基因，并发现41个中的7个与PTSD显著相关（p< 0.05），其中一个（ATP 6AP 1L）在多重检验校正中幸存下来。对于发现数据中涉及的整个基因组，发现和复制样品之间也存在广泛的重叠证据，这是基于效应方向和p < 0.05显著探针的富集，超出了在无效情况下的预期。最后，我们发现来自发现样本的差异表达基因的集合富集了对糖皮质激素信号传导有反应的基因，与对照相比，大多数在PTSD病例中显示出降低的表达。
We examined the association between posttraumatic stress disorder (PTSD) and gene expression using whole blood samples from a cohort of trauma-exposed white non-Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and gene transcripts were analyzed. We found 41 that were differentially expressed in PTSD cases versus controls (multiple-testing correctedp< 0.05). The most significant wasDSCAM, a neurological gene expressed widely in the developing brain and in the amygdala and hippocampus of the adult brain. We then examined the 41 differentially expressed genes in a meta-analysis using two replication cohorts and found significant associations with PTSD for 7 of the 41 (p< 0.05), one of which (ATP6AP1L) survived multiple-testing correction. There was also broad evidence of overlap across the discovery and replication samples for the entire set of genes implicated in the discovery data based on the direction of effect and an enrichment ofp< 0.05 significant probes beyond what would be expected under the null. Finally, we found that the set of differentially expressed genes from the discovery sample was enriched for genes responsive to glucocorticoid signaling with most showing reduced expression in PTSD cases compared to controls.