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，并显著降低了肾移植患者的死亡率。 KT受体的生存和生活质量。KT是一种非常有限的资源， 移植计划来预测KT术后并发症。然而，重度抑郁症（MDD）和抑郁症后 创伤性应激障碍（PTSD）在KT接受者中的患病率均为20%。这项工作的首要目标是， 一项计划是系统地研究MDD和PTSD的基因组、临床和心理社会因素 在KT之后具体目标是：1）生成一个回顾性的基于电子健康记录的KT队列 接受者描述KT后精神障碍的生物心理社会风险因素; 2）建立一个 KT候选人的前瞻性队列，以跟踪精神症状和风险因素的轨迹;以及3） 开发KT接受者精神障碍的预测模型。肾脏疾病不成比例地影响 传统少数民族，大多数接受KT的人不是欧洲血统。计算遗传风险评分时 对于KT接受者，我将利用新的和多样化的训练集和不断增长的基因组方法工具包， 适当地估计整个祖先的遗传风险。我预计这项工作将提高我们的能力， 更广泛地了解和减轻肾病患者的精神疾病风险， 将基因组数据应用于非欧洲血统的患者。 博士纳什是一位医生科学家，她深深致力于她的主要职业目标，即改善人们的心理健康。 重症患者，重点是那些等待或生活在固体器官移植。她的长期 研究目标是建立具有基因组数据的临床登记，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，这将为未来的个性化，靶向和预 对那些有精神共病风险的人进行积极治疗。纳什博士拥有生物化学博士学位， 一个强大的科学背景，是一个奖学金培训的精神科医生，现在需要在临床研究的培训 和精神遗传学来实现她作为一个独立资助的研究者的目标。该研究概述了 在本提案中，将提供以下方面的必要培训：1）设计、管理和统计分析 临床数据库; 2）在前瞻性队列研究期间捕获心理特征的调查方法;以及 3)GWAS数据解释和遗传风险评分的计算。纳什博士建立了一个核心导师团队 由Samantha Meltzer-Brody博士（联合首席导师）组成，他是一位医生兼科学家， 情绪障碍专家;帕特里克沙利文博士（联合首席导师），世界著名的精神病遗传学家;云博士 李（共同导师），统计遗传学家谁开发的核心方法，基因组学，包括填补和 遗传协会;和大卫格伯博士（共同导师），腹部移植主任在华盛顿大学谁拥有 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 患者他们的联合指导将使纳什博士成功地作为一个独立的调查员。

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.