Genetic and Epigenetic Dissection of PTSD in African American Veterans

非裔美国退伍军人 PTSD 的遗传和表观遗传剖析

基本信息

批准号：
8925363
负责人：
JEAN C. BECKHAM
金额：
--
依托单位：
DURHAM VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8925363
关键词：
Accounting Address Affect Afghanistan African American Age Anxiety Disorders Biological Markers Candidate Disease Gene Case-Control Studies Chronic Comorbidity Complex DNA DNA Methylation Data Data Set Diagnosis Dissection Environment Environmental Exposure Environmental Risk Factor Epigenetic Process Exposure to Failure Family Study Funding Agency Gender Genes Genetic Genetic Markers Genetic Models Genetic Variation Genome Genotype High Prevalence Individual Ions Iraq Knowledge Life Light Measures Mental Depression Mental disorders Methylation Military Personnel Modeling Patients Population Post-Traumatic Stress Disorders Predisposition Research Risk Role Sampling Severities Site Social support Statistical Models Stress Substance abuse problem Testing Trauma Twin Studies Unemployment Variant Veterans Woman bead chip case control disorder risk epigenetic profiling epigenetic variation epigenome gene environment interaction genetic association genetic variant genome wide association study improved innovation men pediatric trauma physical conditioning public health relevance pyrosequencing resilience response risk variant

项目摘要

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) is a complex anxiety disorder that develops following exposure to either military or civilian traumatic stress. PTSD affects approximately 10% of women and 5% of men in the US, and affected individuals are at increased risk for unemployment, depression, substance abuse, and impaired physical health. PTSD is overrepresented in Veterans. Family and twin studies have implicated both genetic and environmental factors in PTSD risk. Case/control studies have identified associations between PTSD risk and variants in a number of candidate genes; however, such associations have not been consistently replicated in multiple independent datasets. We hypothesize that this difficulty in replication is the result of the failure of previous studies to include epigenetic variation, an to fully account for gene/environment interactions. The present application will address this gap in our knowledge of the factors that increase risk of PTSD. We have an existing genome-wide association dataset of more than 2500 PTSD cases and controls (including 1470 African Americans), genotyped at more than 2.5 million genetic variants. We will conduct association studies in this dataset, and incorporate environmental influences in our genetic models. We will measure epigenetic variation in 1470 African American PTSD patients and controls, using the Illumina methylation arrays that measure DNA methylation levels at more than 480,000 sites across the genome. This methylation data will be analyzed independently, as well as in conjunction with genetic data, to determine its role in PTSD risk. Finally, we will conduct an exploratory gene*environment and epigenome*environment interaction analysis. By including environmental and epigenetic factors in our analysis of genetic variants, we stand to gain a much clearer understanding of the multiple factors that increase both the risk and severity of PTSD.

描述（由申请人提供）：创伤后应激障碍（PTSD）是一种复杂的焦虑症，在暴露于军事或平民创伤性压力后发展。 PTSD影响美国约10％的女性和5％的男性，受影响的个体患有失业，抑郁症，滥用药物和身体健康的风险增加。 PTSD在退伍军人中的代表过多。家庭和双胞胎研究已经在PTSD风险中实施了遗传和环境因素。病例/对照研究已经确定了许多候选基因中PTSD风险与变异的关联。但是，此类关联并未在多个独立数据集中始终如一地复制。我们假设复制的困难是先前研究未能包括表观遗传变异的结果，这是完全解释基因/环境相互作用的结果。本应用程序将在我们了解增加PTSD风险的因素的情况下解决这一差距。我们拥有2500多个PTSD病例和对照组（包括1470名非裔美国人）的现有基因组关联数据集，其基因型超过250万个遗传变异。我们将在此数据集中进行关联研究，并将环境影响纳入我们的遗传模型。我们将使用Illumina甲基化阵列测量1470名非裔美国PTSD患者和对照组的表观遗传变异，该阵列测量了整个基因组超过480,000个位点的DNA甲基化水平。该甲基化数据将独立分析以及与遗传数据一起分析，以确定其在PTSD风险中的作用。最后，我们将进行探索性基因*环境和表观基因组*环境相互作用分析。通过在我们对遗传变异的分析中包括环境和表观遗传因素，我们将对增加PTSD风险和严重程度的多种因素获得更清晰的了解。