A Twin Study of Chronic Back Pain and Associated Disability in Veterans

退伍军人慢性背痛和相关残疾的双胞胎研究

• 批准号: 9172623
• 负责人: Pradeep Suri
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9172623
• 关键词: Address; Area; Back Pain; Bioinformatics; Biological; Characteristics; Chronic; Clinical; Clinical Medicine; Comorbidity; Controlled Study; DNA Methylation; DNA Sequence; Data; Databases; Development; Disease; Ensure; Environment; Environmental Risk Factor; Epidemiologic Studies; Epigenetic Process; Etiology; Family; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Heritability; High Prevalence; Incidence; Information Centers; Intervention; Leadership; Learning; Mental Health; Mental disorders; Mentors; Mentorship; Military Personnel; Modeling; Monozygotic twins; Outcomes Research; Pain; Pain Research; Pain management; Pathway interactions; Physiatrist; Physical Function; Population; Post-Traumatic Stress Disorders; Predisposition; Prevention; Production; Registries; Rehabilitation therapy; Research; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Sampling; Science; Structure; Symptoms; Training; Twin Multiple Birth; Twin Studies; Universities; Variant; Veterans; Vietnam; Vietnam Conflict; Washington; base; biobank; career; chronic back pain; chronic pain; clinical care; clinical epidemiology; cohort; comparative effectiveness; cost; design; disability; effective intervention; epigenetic marker; epigenome; epigenome-wide association studies; experience; family genetics; genetic epidemiology; hands-on learning; improved functioning; insight; male; meetings; member; methylation pattern; non-genetic; novel; pain rehabilitation; physical conditioning; public health relevance; skills; success; symposium; therapy development

DESCRIPTION: Pain management has been identified as a priority area in VA clinical care, and chronic back pain is a leading cause of disability for US veterans. The role in back pain of psychiatric disorders such as post- traumatic stress disorder (PTSD) has not been well studied in Veterans. For example, while there is a high co-occurrence of PTSD with chronic pain in Veterans, it remains unknown whether PTSD is a risk factor for the development of pain, or whether this co-occurrence is due to other factors such as shared familial predispositions. In addition, there have been no studies to date examining the genomics of back pain in Veterans. We propose a study of back pain in older Veterans who are members of the Vietnam Era Twin (VET) Registry. The Registry is comprised of 7369 male-male twin pairs, both of whom served in the military during the Vietnam conflict (1964-1975). We will capitalize on the rich data available in the Registry, and the recently completed study entitled, 'CSP 569: A Twin Study of the Course and Consequences of PTSD in Vietnam Era Veterans'. Our project consists of 3 interrelated components. First, we will analyze detailed information on PTSD and back pain from amongst the 7332 veterans who participated in CSP 569. Second, we will follow 171 MZ twin pairs who are discordant for PTSD symptoms, but are concordant for absence of back pain at baseline, for the occurrence of back pain. The longitudinal MZ co-twin design allows examination of the effect of an exposure while controlling for shared genetics and family environment. Third, we will conduct an epigenome-wide association study (EWAS) identifying differentially methylated regions (DMRs) associated with prevalent chronic back pain and back pain risk factors using recently acquired biospecimens from the VET Registry Biorepository. We will further cross-reference identified DMRs with existing databases of genes associated with known pain mechanisms, and conduct pathway analyses to identify specific biological networks which may be implicated in the production of pain. The candidate, Dr. Pradeep Suriyaarachchi, MD, MS is a physiatrist with subspecialty training in Pain Medicine and clinical expertise in back pain management. His career goal is to become an independent VA Investigator conducting epidemiologic research focused on the prevention of back pain, and improving function for Veterans with chronic back pain. His background is in clinical epidemiology, but he seeks to gain training in contemporary genetic epidemiology, genomics, and bioinformatics, in order to gain insights into the etiology of back pain, and to develop new interventions for back pain and related disability. He has assembled an outstanding mentorship team under the leadership of primary mentor Dr. Edward Boyko, MD, MPH. This mentorship team includes renowned experts in clinical epidemiology, genetic epidemiology, genomics, and bioinformatics, as well as the clinical domains of back pain and rehabilitation. The CDA-2 will allow Dr. Suriyaarachchi the structured coursework, mentorship, and applied learning needed to acquire new research skills in genetic epidemiology and genomics. Structured learning experiences will include formal coursework and seminars, regular local conferences, and attendance at scientific meetings. He will take advantage of key local resources to carry out the proposed research and training in the centers where his mentors are based, including the VA Seattle Epidemiologic Research and Information Center (where he is an investigator), the VET Registry, and the University of Washington's Department of Genome Sciences and Comparative Effectiveness, Cost, and Outcomes Research Center (which specializes in back pain research). This outstanding local environment will help ensure Dr. Suriyaarachchi's success.

描述： 疼痛管理已被确定为退伍军人管理局临床护理的优先领域，慢性背痛是美国退伍军人残疾的主要原因。退伍军人中尚未充分研究创伤后应激障碍 (PTSD) 等精神疾病在背痛中的作用。例如，虽然退伍军人中 PTSD 与慢性疼痛同时发生的比例很高，但目前尚不清楚 PTSD 是否是发生疼痛的危险因素，或者这种同时发生是否是由于其他因素（例如共同的家族倾向）造成的。 。此外，迄今为止还没有研究检查退伍军人背痛的基因组学。我们提议对越南时代双胞胎 (VET) 登记处的老年退伍军人进行一项背痛研究。该登记处由 7369 对男性对男性双胞胎组成，他们都在越南冲突期间（1964-1975 年）在军队服役。我们将利用登记处提供的丰富数据以及最近完成的题为“CSP 569：越战时期退伍军人 PTSD 的过程和后果的双胞胎研究”的研究。我们的项目由 3 个相互关联的部分组成。首先，我们将分析参加 CSP 569 的 7332 名退伍军人中关于 PTSD 和背痛的详细信息。其次，我们将跟踪 171 对同卵双胞胎，他们的 PTSD 症状不一致，但基线时没有背痛，对于腰痛的发生。纵向 MZ 双胞胎设计允许检查暴露的影响，同时控制共同的遗传和家庭环境。第三，我们将使用最近从 VET 注册生物存储库获得的生物样本进行全表观基因组关联研究 (EWAS)，识别与流行的慢性背痛和背痛危险因素相关的差异甲基化区域 (DMR)。我们将进一步将已确定的 DMR 与已知疼痛机制相关基因的现有数据库进行交叉引用，并进行通路分析，以确定可能与疼痛产生有关的特定生物网络。候选人 Pradeep Suriyaarachchi 博士（医学博士、理学硕士）是一位理疗师，接受过疼痛医学亚专业培训，并拥有背痛管理方面的临床专业知识。他的职业目标是成为一名独立的退伍军人事务部调查员，开展流行病学研究，重点是预防背痛，并改善患有慢性背痛的退伍军人的功能。他的背景是临床流行病学，但他寻求获得当代遗传流行病学、基因组学和生物信息学方面的培训，以便深入了解背痛的病因，并开发针对背痛和相关残疾的新干预措施。他在主要导师Edward Boyko博士（医学博士、公共卫生硕士）的领导下组建了一支优秀的导师团队。该导师团队包括临床流行病学、遗传流行病学、基因组学、生物信息学以及背痛和康复临床领域的知名专家。 CDA-2 将为 Suriyaarachchi 博士提供获得遗传流行病学和基因组学新研究技能所需的结构化课程、指导和应用学习。结构化的学习体验将包括正式的课程和研讨会、定期的当地会议以及参加科学会议。他将利用当地的关键资源，在其导师所在的中心开展拟议的研究和培训，包括 VA 西雅图流行病学研究和信息中心（他是该中心的研究员）、VET 登记处和大学华盛顿基因组科学系和比较有效性、成本和结果研究中心（专门从事背痛研究）。当地优越的环境将有助于确保 Suriyaarachchi 博士的成功。