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

项目摘要/摘要 在全球范围内，神经精神障碍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，对少数民族精神障碍的理解仍然存在主要限制 人口，特别是混合血统的“混合”群体。由于缺乏方法论方法， 考虑到他们额外的基因组复杂性，混合种群被系统地排除在精神病学之外 基因组研究。混血人口，包括非裔美国人和拉丁裔人，占三分之一以上 有更高的焦虑症发病率，包括创伤后应激障碍，但这些群体面临着严重的 由于在精神病学基因组学中的代表性严重不足，精神健康研究和治疗方面的差异。 要从包括我们所有人、NeuroGAP和PGC在内的努力中获得充分和公平的好处，还有一个紧迫的未得到满足的问题 需要开发工具来研究混血人群的精神特征。 候选人建议通过开发一套统计方法、软件包、 和分析资源。阿特金森博士将：建立一种工具，允许混杂的个体融入 精神病学GWAS；1b)聚集显著扩大的美洲原住民参考小组以改善基因组 在混合美国人群中的推断；2a)表征与精神疾病有关的特征的遗传基础 在最大的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 改善个体精细图谱；以及3)开发一种统计方法，产生可靠的遗传风险分数 关于混合受试者的精神特征。这些努力填补了现有资源的主要缺口，并将改善我们的 对不同群体的精神疾病的理解，医学基因组学迄今未能做到这一点。这些努力是 与NIMH的战略使命直接一致，突出了拟议项目的关键和及时性质。 拟议的研究和培训计划经过精心设计，以提供三个领域的专门知识：1) 精神障碍的表型和遗传结构，2)统计方法的发展，3) 职业发展。这些技能对于候选人成为一名领先的调查员的目标来说是至关重要的 世卫组织开发和应用统计基因组学来了解不同人群的精神疾病。在……里面 除了研究培训，阿特金森博士还将参加课程作业，定期参加研讨会，参加研讨会和 参加会议，并在当地和非洲获得指导和教学经验。所有研究都将在 马萨诸塞州总医院、布罗德研究所和哈佛大学的分析和翻译遗传学部门 陈冯富珍公共卫生学院，由著名科学家马克·戴利博士和卡雷斯坦·科宁博士指导。 来自领先专家Ben Neale博士、Alkes Price博士和Jordan Smoller博士的其他指导将确保出类拔萃 指导和支持。总体来说，培训环境优秀，导师和顾问都是世界一流的， 拟议的研究解决了一个紧急的未得到满足的需求，在这个奖项中获得的额外技能将使Dr。 阿特金森将在人口、统计和精神病学基因组学领域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.