A framework enabling the genomic analysis of psychiatric traits across admixed populations.

项目概要/摘要 在全球范围内，神经精神疾病是导致残疾的主要原因。尽管最近在心理健康方面取得了进展 遗传学在欧亚人群中，主要的局限性仍然存在于少数民族精神疾病的理解。 人口，特别是混合血统的“混合”群体。由于缺乏方法， 考虑到他们额外的基因组复杂性，混合人群被系统地排除在精神病学之外。 基因组研究包括非裔美国人和拉丁美洲人在内的混血人口占三分之一以上 美国人口中有50%的人患有一些焦虑症，包括创伤后应激障碍，但这些群体面临严重的 由于在精神病基因组学中的代表性严重不足，心理健康研究和治疗存在差异。 为了从我们所有人，NeuroGAP和PGC的努力中获得充分和公平的利益，有一个紧迫的未满足的问题。 需要开发工具，允许在混合人群的精神病学特征的研究。 候选人建议通过开发一套统计方法、软件包， 分析资源。阿特金森博士将：1a）建立一个工具，允许混合个体的整合， 精神病GWAS; 1b）聚集一个显着扩大的美洲原住民参考小组，以改善基因组 在混合的美国人群中的推断; 2a）描述与精神病相关的特征的遗传基础 最大生物库数据集的不同人群中的疾病; 2b）利用混合中的连锁不平衡 个体，以改善精细映射;和3）开发一种统计方法，产生可靠的遗传风险评分 混合实验对象的精神特征这些努力填补了现有资源的一个重大缺口，并将改善我们的 医学基因组学迄今未能在不同群体中理解精神疾病。这些努力 与NIMH的战略使命直接一致，突出了拟议项目的关键性和及时性。 拟议的研究和培训计划是精心设计的，旨在提供三个领域的专业知识： 精神疾病的表型和遗传结构，2）统计方法的发展，以及3） 专业发展。这些技能是候选人成为主要调查员的基本目标 世卫组织开发并应用统计基因组学来了解不同人群的精神疾病。在 除了研究培训，阿特金森博士将参加课程，参加定期研讨会，参加讲习班， 会议，并在当地和非洲获得导师和教学经验。所有研究将在 马萨诸塞州总医院、布罗德研究所和哈佛TH的分析和翻译遗传学单位 Chan公共卫生学院，由著名科学家Mark Daly博士和Karestan Koenen博士指导。 来自顶尖专家本·尼尔博士，Alkes Price和Jordan Smoller的额外指导将确保卓越的 指导和支持。总的来说，培训环境是杰出的，导师和顾问是世界一流的， 这些研究项目解决了一个迫切的未满足的需求，而在这个奖项中获得的额外技能将使Dr。 阿特金森在人口，统计和精神病基因组学方面建立独立的领导地位。

PROJECT SUMMARY/ABSTRACT Globally, neuropsychiatric disorders are the leading cause of disability. Despite recent advances in mental health genetics in Eurasian groups, major limitations remain in the understanding of psychiatric disorders in minority populations, in particular “admixed” groups of mixed ancestry. Due to the paucity of methodological approaches that account for their additional genomic complexity, admixed populations are systematically excluded from psychiatric genomic studies. Admixed populations, including African American and Latino individuals, make up more than a third of the US populace and have higher rates of some anxiety disorders including PTSD, yet these groups face severe disparities in mental health research and treatment due to being so sorely underrepresented in psychiatric genomics. To reap full and equitable benefits from efforts including All of Us, NeuroGAP, and the PGC, there is a pressing unmet need for the development of tools permitting the study of psychiatric traits in admixed peoples. The candidate proposes to address this issue by developing a suite of statistical methods, software packages, and analytical resources. Dr. Atkinson will: 1a) build a tool to allow for the integration of admixed individuals into psychiatric GWAS; 1b) aggregate a significantly expanded Native American reference panel to improve genomic inference in admixed American populations; 2a) characterize the genetic basis of traits relevant to psychiatric disorders in diverse populations of the largest biobank dataset; 2b) leverage the linkage disequilibrium in admixed individuals to improve fine-mapping; and 3) develop a statistical method that generates reliable genetic risk scores for psychiatric traits in admixed subjects. These efforts fill a major gap in existing resources and will improve our understanding of psychiatric diseases in diverse groups whom medical genomics has so far failed. These efforts are in direct line with the strategic mission of the NIMH, highlighting the crucial and timely nature of the proposed project. The proposed research and training plan were carefully designed to confer expertise in three domains: 1) phenotypes and genetic architectures of psychiatric disorders, 2) statistical methods development, and 3) professional development. These skills are fundamental to the candidate’s goal of becoming a leading investigator who develops and applies statistical genomics to understand psychiatric disorders across diverse populations. In addition to research training, Dr. Atkinson will take coursework, participate in regular seminars, attend workshops and conferences, and gain mentorship and teaching experience locally and in Africa. All research will be conducted in the Analytic and Translational Genetics Unit at Massachusetts General Hospital, the Broad Institute, and the Harvard TH Chan School of Public Health with mentorship from renowned scientists Drs. Mark Daly and Karestan Koenen. Additional guidance from leading experts Drs. Ben Neale, Alkes Price, and Jordan Smoller will ensure exceptional guidance and support. Overall, the training environment is outstanding, the mentors and advisors are world-class, the proposed studies address an urgent unmet need, and the additional skills gained in this award will poise Dr. Atkinson to establish independent leadership in population, statistical, and psychiatric genomics.