Mark W Miller1, Erika J Wolf2, Mark W Logue3, Clinton T Baldwin4. 1. National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. Electronic address: mark.miller5@va.gov. 2. National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. 3. Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. 4. Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND: 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. METHODS: 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: 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. LIMITATIONS: The primary limitations were the modest size of the cohort and the absence of a replication sample. CONCLUSIONS: 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. Published by Elsevier B.V.
BACKGROUND: 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. METHODS: 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: 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. LIMITATIONS: The primary limitations were the modest size of the cohort and the absence of a replication sample. CONCLUSIONS: 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. Published by Elsevier B.V.
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