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

• 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
• 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

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.

项目摘要 /摘要 该应用程序的广泛目标是建立一项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革命受益于非洲人的子孙后代。大步很大 我们是为了理解精神分裂症的遗传结构。最终这些进步将 在减少全球精神疾病的伯恩伯恩方面发挥着关键作用。但是，非洲人口有 我们几乎没有神经精神遗传学研究，这给这两种科学带来了挑战 进步和全球公平。来自非洲人口的数据在神经精神疾病的遗传研究中 至关重要的是遗传危险因素的完整情况并确定潜在缺失的新型治疗 通过研究所有人群而获得的信号。非洲人口中标记之间的相关性降低 也可用于精细的映射引起疾病的等位基因。除了发现之外，最近关于多基因风险得分的工作 表明这些措施的临床实用性的潜力，但令人烦恼的是，跨种群有限 可转移性和扩展性较差的未表征人群（例如来自非洲的人群）的性能较差。 最新的神经精神遗传学进展也有很大的风险将导致扩大 非洲与世界其他地区之间的大规模研究和治疗差异。弥合这个差距， 我们已经启动了Neurogap-Psychosis项目，这是与亚的斯亚贝巴大学的同事合作 在埃塞俄比亚，乌干达的马克塞雷大学和南非开普敦大学，目的是 建立跨国神经精神遗传学研究和培训计划 哈佛T.H.陈公共卫生学院实现以下特定目标：1）能力建设。 扩大非洲科学家进行精神分裂和其他大规模遗传研究的能力 精神病疾病可以在本地对这些数据的生成，分析和解释； 2）临床 表征。验证用于精神分裂症和精神病的诊断和筛查的工具。系统地 表征13,000例精神分裂症和精神病患者的临床现象学， 包括风险因素，症状表现，严重程度，用药，药物使用和合并症 状况; 3）遗传发现。对非洲精神分裂症进行最大的基因发现研究 日期。在与当地研究人员的合作中，我们将进行全基因组协会研究 祖先相似的病例/对照人群中的精神分裂症。该建议直接解决了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。”我们的 广泛的目标是制定旨在解决主要限制的可持续研究和培训计划 在我们了解精神疾病的遗传和环境风险建筑中 非洲血统并导致非洲和所有人群的诊断，预防和治疗改善。