Genetics of PTSD and Trauma-Related Drinking

创伤后应激障碍和创伤相关饮酒的遗传学

• 批准号: 9327490
• 负责人: Sage Elyse Hawn
• 金额: $ 3.53万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-10 至 2020-04-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9327490
• 关键词: Alcohol Phenotype; Alcohol abuse; Alcohol consumption; Alcohol dependence; Area; Award; Bioinformatics; Biological; Clinical; Comorbidity; Complex; Data; Development; Diagnostic; Disease; Emerging Technologies; Etiology; Foundations; Genes; Genetic; Genetic Predisposition to Disease; Genetic Research; Genetic Risk; Genetic Variation; Goals; Heritability; Hypothalamic structure; Immune response; Individual; Interdisciplinary Study; Intervention; Investigation; Joints; Knowledge; Link; Literature; Longitudinal Studies; Longitudinal cohort study; Measures; Mediating; Mentors; Mind; Mission; Modeling; Molecular; Molecular Genetics; National Institute on Alcohol Abuse and Alcoholism; National Research Service Awards; Outcome; Parents; Participant; Pathway Analysis; Pathway interactions; Phenotype; Pituitary-Adrenal System; Population; Post-Traumatic Stress Disorders; Prevalence; Prevention; Preventive Intervention; Public Health; Recording of previous events; Recruitment Activity; Research; Research Personnel; Research Training; Risk; Sampling Studies; Science; Self Medication; Severities; Societies; Solid; Stress; Stress and Coping; Study models; Symptoms; Techniques; Testing; Time; Training; Trauma; Twin Multiple Birth; Twin Studies; Universities; Variant; aged; aging population; alcohol abuse therapy; alcohol use disorder; clinically relevant; college; coping; cost; disorder risk; drinking; drinking behavior; experience; follow-up; genetic analysis; genome wide association study; genome-wide; high risk; high risk drinking; improved; new technology; novel; psychosocial; risk sharing; skill acquisition; sound; stress disorder; study population; tool; trait; university student; young adult

PROJECT SUMMARY Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are prevalent, costly to society, and frequently co-occur. In fact, nearly half of individuals in treatment for AUD meet diagnostic criteria for current PTSD. Both AUD and PTSD are moderately heritable and have overlapping latent genetic risk; however, etiological models examining the shared risk between these phenotypes are lacking. The drinking to cope self- medication model is a promising paradigm to inform research in this area. Although it is well accepted that coping-oriented drinking is linked with problematic alcohol use and increased likelihood of AUD, there is a paucity of research examining drinking to cope with trauma-related symptoms specifically. To date, there are no studies, phenotypic or genetic, on trauma-related drinking to cope. The present study seeks to fill this void by leveraging a genetically informative longitudinal cohort study from a large urban university (NIAAA-R37 AA011408) in order to achieve three primary aims: 1) examine the relationships between AUD symptoms, trauma-related drinking to cope, and PTSD symptoms and determine if trauma-related drinking to cope mediates the relationship between PTSD and AUD symptoms; 2) examine genetic variation (i.e., genome wide association [GWA] analyses) and aggregate risk (i.e., genome wide complex trait analyses [GCTA], polygenic risk score [PRS]) associated with trauma-related drinking, PTSD, and shared variation between the two phenotypes; and 3) apply bioinformatics tools to investigate genetic pathways associated with, and probable overlap between, trauma-related drinking and PTSD. The results of this study will aid in elucidating shared genetic influences underlying trauma-related drinking and PTSD, an area which remains poorly understood. The ability to identify individuals with higher biological risk for trauma-related drinking and PTSD will inform targeted prevention and integrative intervention strategies, particularly among individuals at increased psychosocial risk for problematic alcohol use and PTSD, such as college-age populations. The proposed NRSA study has been developed with four specific training goals in mind: 1) develop expertise in the empirical study of trauma-related phenotypes (e.g., AUD, trauma-related drinking, PTSD); 2) gain a solid foundation in molecular and statistical genetics; 3) gain knowledge and experience in bioinformatics techniques, such as genetic pathway analyses; and 4) further cultivate professional development skills that will enhance the candidate’s background in support of becoming a knowledgeable and well-rounded academic researcher. These research and training aims reflect the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) mission, which emphasizes clinically relevant, transdisciplinary research, as well as directly align with the NIAAA Strategic Objective to “identify genes associated with vulnerability for alcohol dependence by employing new and emerging technologies, particularly on samples from study populations previously recruited for genetic research on alcohol dependence.” !

项目摘要 酒精使用障碍（AUD）和创伤后应激障碍（PTSD）是普遍存在的，对社会来说代价高昂， 经常发生。事实上，近一半接受AUD治疗的患者符合目前的诊断标准。 创伤后应激障碍AUD和PTSD都是中度遗传的，并且具有重叠的潜在遗传风险;然而， 缺乏检查这些表型之间共同风险的病因学模型。喝酒是为了自我安慰 药物模型是一个很有前途的范例，为这一领域的研究提供信息。尽管大家都认为 以应对为导向的饮酒与有问题的酒精使用和AUD的可能性增加有关， 缺乏专门研究饮酒以科普创伤相关症状的研究。迄今已有 没有研究，表型或遗传，对创伤相关的饮酒，以科普。本研究报告力求填补这一空白 利用一个大型城市大学的遗传信息纵向队列研究（NIAAA-R37 AA 011408），以实现三个主要目的：1）检查AUD症状之间的关系， 创伤相关的饮酒，以科普，和创伤后应激障碍的症状，并确定是否创伤相关的饮酒，以科普 介导PTSD和AUD症状之间的关系; 2）检查遗传变异（即，全基因组 关联[GWA]分析）和总风险（即，全基因组复杂性状分析 风险评分[PRS]）与创伤相关的饮酒，PTSD，以及两者之间的共享变异 表型;和3）应用生物信息学工具来研究与可能的 与创伤有关的饮酒和创伤后应激障碍之间的重叠。这项研究的结果将有助于阐明共享 遗传影响潜在的创伤相关的饮酒和创伤后应激障碍，一个领域仍然知之甚少。 识别与创伤有关的饮酒和创伤后应激障碍的生物风险较高的个体的能力将告知 有针对性的预防和综合干预战略，特别是在日益严重的 有问题的酒精使用和创伤后应激障碍的心理社会风险，如大学年龄段的人群。 拟议的NRSA研究的制定考虑了四个具体的培训目标：1）制定 创伤相关表型的经验研究的专业知识（例如，AUD，创伤相关饮酒，PTSD）; 2） 获得分子和统计遗传学的坚实基础; 3）获得知识和经验， 生物信息学技术，如遗传途径分析;以及4）进一步培养专业人员 发展技能，这将提高候选人的背景，支持成为一个知识渊博， 全面的学术研究者这些研究和培训目标反映了国家酒精研究所 滥用和酒精中毒（NIAAA）的使命，强调临床相关，跨学科的研究， 并直接与NIAAA战略目标保持一致，以“识别与脆弱性相关的基因， 通过采用新的和新兴的技术，特别是对研究样本的酒精依赖 这些人以前曾被招募用于酒精依赖的遗传研究。 !