Analysis of RORA and other candidate genes in PTSD

RORA和PTSD其他候选基因分析

• 批准号: 8541545
• 负责人: MARK W MILLER
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541545
• 关键词: Accidents; Address; Affect; American Psychiatric Association; Attention deficit hyperactivity disorder; Autistic Disorder; Behavioral; Binding; Biochemical; Bioinformatics; Bipolar Disorder; Blood; Candidate Disease Gene; Circadian Rhythms; Cognitive; Collection; Comorbidity; Complement; DNA Sequence; DSM-IV; Data; Development; Diagnosis; Disasters; Disease; Emotional; Emotions; Event; Exposure to; Forcible intercourse; Fright; Gene Expression Profile; Gene Expression Profiling; General Population; Genes; Genetic; Genetic Variation; Genotype; Heredity; Heritability; Individual; Injury; Life; Light; Lymphocyte; Mental Depression; Mental disorders; Military Personnel; Molecular; Molecular Genetics; NR1 gene; Nightmare; Nuclear Hormone Receptors; Orphan; Paper; Pathway interactions; Phenotype; Physiological; Play; Post-Traumatic Stress Disorders; Probability; Process; Proteins; Psychophysiology; Publishing; RNA; Reporting; Research; Retinoids; Risk; Risk Factors; Role; Single Nucleotide Polymorphism; Sleep; Stimulus; Stress; Symptoms; Thinking; Trauma; Twin Multiple Birth; Twin Studies; Variant; Veterans; Violence; base; brain cell; combat; disorder risk; experience; follow-up; functional genomics; gene interaction; genetic analysis; genetic risk factor; genetic variant; genome wide association study; genome-wide; hormone regulation; hormone response element; meetings; member; neuroprotection; novel; physical assault; public health relevance; receptor; response; sexual assault

DESCRIPTION (provided by applicant): Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder characterized by profound disturbances in cognitive, behavioral and physiological functioning that occurs following exposure to a psychologically traumatic event. After exposure, the probability of developing PTSD is estimated to be approximately 10% in the general population, although higher rates (i.e., closer to 25%) have been observed among combat Veterans. Numerous factors contribute to the probability of developing the disorder including heredity. Twin studies have shown that a 30-70% of variation in PTSD risk is explained by genetic factors. In a recent paper (Logue et al, 2012); we reported results from the first published genome-wide association study (GWAS) for PTSD. We found that single nucleotide polymorphisms (SNPs) in the retinoid-related orphan receptor alpha (RORA) gene showed genome-wide significant associations with PTSD suggesting that this gene is an important risk locus for the disorder. RORA has been implicated in prior psychiatric GWAS as a risk factor for attention-deficit hyperactivity disorder, bipolar disorder, autism, and depression. The gene is also known to influence circadian rhythms, hormone regulation, and neuroprotection. Based on this, we believe that our finding implicating RORA in the development PTSD may point to a new and potentially important avenue for future research on the disorder. Therefore, the aim of the proposal is to conduct a more detailed genetic analysis of RORA and PTSD. Specifically, we propose to conduct extensive sequencing of RORA (along with several other PTSD candidate genes) to identify the complete array of genetic variation in these genes associated with PTSD risk and then perform genome- wide expression analysis using blood lymphocyte RNA. We also aim to follow-up our GWAS finding with analysis of additional PTSD-related comorbidity phenotypes and examination of possible gene-gene interactions. Findings are expected to shed new light on the role of RORA and other candidate genes on the development of PTSD.

描述（由申请人提供）：