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

一个能够对混合人群的精神特征进行基因组分析的框架。

• 批准号: 10405367
• 负责人: Elizabeth Grace Atkinson
• 金额: $ 17.44万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405367
• 关键词: Address; Admixture; Affect; Africa; African American; American; Americas; Anxiety Disorders; Area; Attention; Award; Awareness; Clinical; Collection; Complex; Computer software; DNA; Data; Data Collection; Data Set; Development; Development Plans; Educational process of instructing; Educational workshop; Ensure; Environment; Ethnic group; European; Face; General Hospitals; Genetic; Genetic Risk; Genome; Genomics; Genotype; Goals; Haplotypes; Individual; Institutes; Jordan; Latino; Leadership; Linkage Disequilibrium; Maps; Massachusetts; Medical; Medical Genetics; Mental Health; Mental disorders; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Methods; Minority; Minority Groups; Mission; National Institute of Mental Health; Native American Ancestry; Native Americans; Nature; Output; Pattern; Phenotype; Plague; Population; Population Heterogeneity; Positioning Attribute; Post-Traumatic Stress Disorders; Price; Public Health Schools; Race; Research; Research Personnel; Research Training; Resources; Sampling; Scientist; Services; Signal Transduction; Site; Societies; Statistical Methods; Testing; Time; Training; Work; analytical tool; base; biobank; career; cohort; design; disability; disparity reduction; experience; genetic architecture; genome wide association study; health disparity; improved; large scale data; method development; neuropsychiatric disorder; novel; population stratification; psychiatric genomics; psychogenetics; simulation; skills; statistics; symposium; tool; tool development; trait; translational genetics; years lived with disability

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.

项目摘要/摘要 在全球范围内，神经精神疾病是残疾的主要原因。尽管心理健康最近取得了进步 欧亚群体中的遗传学，主要局限性仍然存在于对少数族裔精神疾病的理解 人群，特别是“混合”混合血统的群体。由于缺乏方法论方法 解释其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。包括非裔美国人和拉丁美洲人在内的混合人群构成了三分之一以上的人 在美国民众中，包括PTSD在内的某些焦虑症的发生率更高，但这些群体面临严重的焦虑症 精神病学基因组学中人为差异的差异非常不足。 为了从包括我们所有人，Neurogap和PGC在内的努力中获得充分而公平的收益 需要开发工具，允许在混合人群中研究精神病特征。 通过开发一套统计方法，软件包， 和分析资源。 Atkinson博士将：1A）建立一种工具，允许将混合个人整合到 精神病; 1b）聚集了一个显着扩展的美国原住民参考面板，以改善基因组 推断美国混杂人群； 2a）表征与精神病有关的特征的遗传基础 最大生物库数据集的潜水员种群中的疾病； 2b）利用混合的连锁distilebrium 个人以改善精细映射； 3）开发一种产生可靠遗传风险评分的统计方法 对于混合主题的精神病特征。这些努力填补了现有资源的重大空白，将改善我们的 迄今为止，医学基因组学失败的潜水群体中对精神疾病的了解。这些努力是 与NIMH的战略使命直接相符，强调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，以在三个领域的专业知识上进行专业知识：1） 精神病的表型和遗传结构，2）统计方法发展和3） 专业发展。这些技能对于候选人成为领先的调查员的目标至关重要 谁开发和应用统计基因组学来了解潜水员人群的精神疾病。在 除了研究培训外，阿特金森博士还将参加课程工作，参加常规半手，参加研讨会和 会议，并在本地和非洲获得心态和教学经验。所有研究将在 马萨诸塞州综合医院，布罗德研究所和哈佛大学的分析和转化遗传学部门 Chan公共卫生学院拥有著名科学家Drs的遗产。马克·戴利（Mark Daly）和卡雷斯坦·科宁（Karestan Koenen）。 领先专家DRS的其他指导。 Ben Neale，Alkes Price和Jordan Smoller将确保出色 指导和支持。总体而言，培训环境非常出色，导师和顾问是世界一流的， 拟议的研究满足了紧急的未满足需求，该奖项获得的额外技能将毒害博士。 阿特金森（Atkinson）在人群，统计和精神病基因组学方面建立独立的领导力。