Biopsychosocial Risk Factors for Psychiatric Disorders Following Kidney Transplantation

项目摘要 精神障碍在肾移植(KT)后非常普遍，并显著减少 KT受者的生存和生活质量。KT是一种严重有限的资源，并作出了广泛的努力 移植计划，以预测KT后的共病。然而，严重抑郁障碍(MDD)和后抑郁 创伤应激障碍(PTSD)在KT接受者中的患病率都在20%左右。这样做的首要目标是 建议对MDD和PTSD的基因组、临床和心理社会因素进行系统研究 跟随KT。具体目标是：1)生成基于电子健康记录的可追溯的KT队列 接受者描述KT后精神障碍的生物、心理和社会危险因素；2)建立 KT候选人的预期队列，以跟踪精神症状和危险因素的轨迹；以及3) 开发KT受者精神障碍的预测模型。肾脏疾病的影响不成比例 传统少数民族，大多数KT获奖者不是欧洲血统。在计算遗传风险分数时 对于KT接受者，我将利用新的和多样化的培训集以及不断增长的基因组方法工具包来 适当估计不同祖先之间的遗传风险。我预计这项工作将提高我们的能力 更广泛地了解和减少肾脏疾病患者的精神障碍风险，并将 在努力将基因组数据应用于非欧洲血统的患者的基础上。 纳什博士是一名内科科学家，坚定地致力于她的主要职业目标--改善 重病患者，重点是那些等待或与实体器官移植一起生活的人。她的长期工作 研究目标是用基因组数据建立临床登记，以阐明精神疾病的危险因素和病因 实体器官移植受者的疾病，将为个性化、有针对性和预见性的未来理想提供信息 对有精神疾病合并症风险的人进行预防性治疗。纳什博士拥有生物化学博士学位， 有很强的科学背景，是受过奖学金训练的精神病学家，现在需要接受临床研究方面的培训 和精神遗传学来实现她作为一名独立资助的研究人员的目标。这项研究概述了 将在1)设计、管理和统计分析方面提供必要的培训 临床数据库；2)在前瞻性队列研究中捕捉心理特征的调查方法；以及 3)遗传风险评分的数据解释和计算。纳什博士已经建立了一支核心指导团队 由Samantha Meltzer-Brody博士(联合首席导师)组成，她是一位国际公认的内科科学家 情绪障碍专家；帕特里克·沙利文博士(共同导师)，世界著名的精神病学遗传学家；云博士 李(共同导师)，一位统计遗传学家，开发了基因组学的核心方法，包括归因和 和大卫·格伯博士(共同导师)，北卡罗来纳大学腹部移植主任，他有 在该领域广泛发表，包括研究移植的生存益处和长期结果的工作 病人。他们的共同指导将使纳什博士成为一名成功的独立调查员。

Project Summary Psychiatric disorders are highly prevalent following kidney transplantation (KT) and significantly reduce the survival and quality of life of KT recipients. KT is a severely limited resource, and extensive efforts are made by transplant programs to anticipate post-KT co-morbidities. However, major depressive disorder (MDD) and post- traumatic stress disorder (PTSD) both have ~20% point prevalence in KT recipients. The overarching aim of this proposal is to systematically investigate genomic, clinical, and psychosocial contributors to MDD and PTSD following KT. The specific aims are: 1) generate a retrospective electronic health record-based cohort of KT recipients to characterize biopsychosocial risk factors for psychiatric disorders post-KT; 2) establish a prospective cohort of KT candidates to follow trajectories of psychiatric symptoms and risk factors; and 3) develop a predictive model for psychiatric disorders in KT recipients. Kidney disease disproportionately impacts traditional minorities, and most KT recipients are not of European ancestry. When calculating genetic risk score for KT recipients, I will leverage new and diverse training sets and a growing toolkit of genomic methods to appropriately estimate genetic risk across ancestry. I anticipate that this work will improve our ability to understand and mitigate risk of psychiatric disorders for kidney disease patients more broadly and will build on efforts to apply genomic data to patients with non-European ancestry. Dr. Nash is a physician-scientist deeply committed to her primary career goal of improving the mental health of severely ill patients, with an emphasis on those awaiting or living with a solid organ transplant. Her long-term research goal is to build clinical registries with genomic data to elucidate risk factors and etiology of psychiatric disorders in solid organ transplant recipients that will inform the future ideal of personalized, targeted, and pre- emptive treatment for those at risk for psychiatric co-morbidities. Dr. Nash has a PhD in biological chemistry with a strong scientific background, is a fellowship-trained Psychiatrist, and now requires training in clinical research and psychiatric genetics to accomplish her goals as an independently funded investigator. The research outlined in this proposal will provide the necessary training in 1) the design, management, and statistical analysis of clinical databases; 2) survey methodology to capture psychological traits during prospective cohort studies; and 3) GWAS data interpretation and calculation of genetic risk scores. Dr. Nash has built a core mentorship team consisting of Dr. Samantha Meltzer-Brody (co-lead mentor), a physician-scientist and internationally recognized expert in mood disorders; Dr. Patrick Sullivan (co-lead mentor), a world-renowned psychiatric geneticist; Dr. Yun Li (co-mentor), a statistical geneticist who developed core methods for genomics, including imputation and genetic association; and Dr. David Gerber (co-mentor), Chief of Abdominal Transplant at UNC who has published widely in the field including work examining survival benefits and long-term outcomes for transplant patients. Their combined mentorship will allow Dr. Nash to succeed as an independent investigator.