Psychosis Genetics Research in Africa: Building Capacity by Investing in People

非洲精神病遗传学研究：通过投资于人来建设能力

基本信息

批准号：
10005478
负责人：
Dickens Howard Akena
金额：
$ 63.99万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10005478
关键词：
Address Africa African Alcohol or Other Drugs use Alleles Architecture Asians Biological Markers Brain Clinical Clinical Research Collaborations Country Data Data Analyses Diagnosis Disease Ensure Environmental Risk Factor Ethiopia Ethnic group European Funding Future Future Generations Generations Genetic Genetic Research Genetic Risk Genetic study Genome Genomics Goals Haplotypes Health Individual Institutes Institution International Knowledge Lead Longevity Measures Mental disorders Meta-Analysis National Institute of Mental Health Patients Performance Persons Pharmaceutical Preparations Phenotype Play Population Population Control Positioning Attribute Prevention Privatization Psychiatry Psychotic Disorders Public Health Schools Research Research Personnel Research Training Rest Risk Risk Factors Role Schizophrenia Scientific Advances and Accomplishments Scientist Severities Signal Transduction South Africa Strategic Planning Symptoms Training Programs Uganda Universities Variant Work base case control clinical epidemiology cohort comorbidity gene discovery genetic analysis genetic architecture genetic risk factor genetic variant genome wide association study genome-wide molecular targeted therapies nervous system disorder neuropsychiatric disorder neuropsychiatry non-genomic novel therapeutics patient stratification phenomenological models polygenic risk score programs psychiatric genomics psychogenetics screening statistics success tool treatment disparity

项目摘要

PROJECT SUMMARY / ABSTRACT The broad goal of this application is to establish a trans-African neuropsychiatric genetics program that will ensure the genomics revolution in neuropsychiatry benefits future generations of Africans. Great strides have been made in our understanding of the genetic architecture of schizophrenia. Ultimately these advances will play a critical role in reducing the global burden of psychiatric disorders. However, African populations have been almost absent from neuropsychiatric genetics research and this poses a challenge for both scientific advance and global equity. Data from African populations in genetic studies of neuropsychiatric disorders are critical to generate a complete picture of genetic risk factors and identify potentially missing novel therapeutic signals garnered by studying all populations. The reduced correlation between markers in African populations is also useful for fine mapping disease-causing alleles. Beyond discovery, recent work on polygenic risk scores shows that potential for clinical utility of these measures, but also, vexingly, limited cross-population transferability and by extension poorer performance in uncharacterized populations such as those from Africa. There is also a significant risk that the recent advances in neuropsychiatric genetics will result in a widening of the massive research and treatment disparities between Africa and the rest of the world. To bridge this gap, we have initiated the NeuroGAP-Psychosis project, a collaboration with colleagues at Addis Ababa University in Ethiopia, Makerere University in Uganda, and the University of Cape Town in South Africa, with the goal of establishing a multi-national neuropsychiatric genetics research and training program in partnership with the Harvard T.H. Chan School of Public Health to accomplish the following specific aims: 1) Capacity building. Expand the capacity of African scientists to conduct large-scale genetic studies of schizophrenia and other psychotic disorders enabling the generation, analysis and interpretation of these data locally; 2) Clinical characterization. Validate tools for diagnosing and screening for schizophrenia and psychosis. Systematically characterize the clinical phenomenology of 13,000 patients with schizophrenia and psychotic disorders, including risk factors, symptom presentation, severity, medication use, substance use, and comorbid health conditions; 3) Genetic discovery. Perform the largest gene-discovery study of schizophrenia in Africa to date.In collaboration with local investigators, we will conduct genome-wide association studies of schizophrenia in ancestrally similar case/control populations. This proposal directly addresses the NIMH Strategic Plan goal 1.2 “Identify the genomic and non-genomic factors associated with mental illness.” Our broad goal is to develop a sustainable research and training program aimed at addressing the major limitations in our knowledge of the genetic and environmental risk architecture of psychiatric disorders in persons of African descent and lead to improvement in diagnosis, prevention, and treatment in African and all populations.

项目概要/摘要该应用程序的总体目标是建立一个跨非洲神经精神遗传学计划，该计划将确保神经精神病学的基因组学革命造福于非洲的子孙后代。我们对精神分裂症遗传结构的理解最终将得到推进。在减少全球精神疾病负担方面发挥着关键作用。神经精神遗传学研究几乎缺席，这对科学界和科学界都提出了挑战来自非洲人群的神经精神疾病遗传研究的数据是先进和全球公平的。对于全面了解遗传风险因素并识别可能缺失的新疗法至关重要通过研究所有人群收集的信号。非洲人群中标记之间的相关性降低。除了发现之外，最近关于多基因风险评分的工作也可用于精细绘制致病等位基因。表明这些措施具有临床实用性的潜力，但令人烦恼的是，交叉人群有限可转移性以及在非特征人群（例如来自非洲的人群）中表现较差。还有一个重大风险是，神经精神遗传学的最新进展将导致范围扩大。非洲与世界其他地区之间巨大的研究和治疗差距我们启动了 NeuroGAP-Psychosis 项目，这是与亚的斯亚贝巴大学同事合作的项目埃塞俄比亚、乌干达麦克雷雷大学和南非开普敦大学，其目标是与以下机构合作建立多国神经精神遗传学研究和培训计划哈佛大学陈曾熙公共卫生学院要实现以下具体目标： 1) 能力建设。扩大非洲科学家对精神分裂症和其他疾病进行大规模遗传学研究的能力精神障碍能够在本地生成、分析和解释这些数据 2) 临床；系统地验证精神分裂症和精神病的诊断和筛查工具。描述 13,000 名精神分裂症和精神病患者的临床现象学特征，包括风险因素、症状表现、严重程度、药物使用、物质使用和合并症健康状况 3) 进行非洲最大的精神分裂症基因发现研究日期。与当地研究人员合作，我们将进行全基因组关联研究该提案直接针对 NIMH。战略计划目标 1.2“确定与精神疾病相关的基因组和非基因组因素。” 总体目标是制定可持续的研究和培训计划，旨在解决主要局限性根据我们对以下人群精神疾病的遗传和环境风险结构的了解非洲裔并导致非洲和所有人群的诊断、预防和治疗的改善。