National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
J Affect Disord. 2013 Nov;151(2):702-708. doi: 10.1016/j.jad.2013.07.022. Epub 2013 Aug 17.
This study followed on findings from a recent genome-wide association study of PTSD that implicated the retinoid-related orphan receptor alpha (RORA) gene (Logue et al., 2012) by examining its relationship to broader array of disorders.
Using data from the same cohort (N=540), we analyzed patterns of association between 606 single nucleotide polymorphisms (SNPs) spanning the RORA gene and comorbidity factors termed fear, distress (i.e., internalizing factors) and externalizing.
Results showed that rs17303244 was associated with the fear component of internalizing (i.e., defined by symptoms of panic, agoraphobia, specific phobia, and obsessive-compulsive disorder) at a level of significance that withstood correction for gene-wide multiple testing.
The primary limitations were the modest size of the cohort and the absence of a replication sample.
Results add to a growing literature implicating the RORA gene in a wide range of neuropsychiatric disorders and offer new insight into possible molecular mechanisms of the effects of traumatic stress on the brain and the role of genetic factors in those processes.
本研究是在最近一项 PTSD 的全基因组关联研究的发现基础上进行的,该研究通过研究视黄酸相关孤儿受体α(RORA)基因与更广泛的疾病之间的关系,暗示了该基因的作用(Logue 等人,2012 年)。
使用来自同一队列的数据(N=540),我们分析了跨越 RORA 基因的 606 个单核苷酸多态性(SNP)与被称为恐惧、痛苦(即,内在因素)和外在的共病因素之间的关联模式。
结果表明,rs17303244 与内在的恐惧成分有关(即,由恐慌症、广场恐惧症、特定恐惧症和强迫症的症状定义),其关联程度达到了基因广泛多重测试校正后的显著水平。
主要的局限性是队列规模适中,以及缺乏复制样本。
结果增加了越来越多的文献表明 RORA 基因与广泛的神经精神疾病有关,并为创伤应激对大脑的影响的可能分子机制以及遗传因素在这些过程中的作用提供了新的见解。