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: 10443672
• 负责人: Dickens Howard Akena
• 金额: $ 58.82万
• 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/10443672
• 关键词: Address; Africa; African; African ancestry; Alleles; Architecture; Asian ancestry; Biological Markers; Brain; Clinical; Clinical Research; Collaborations; Country; Data; Data Analyses; Diagnosis; Disease; East Asian; 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; Psychoses; 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; risk prediction; screening; statistics; substance use; 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.

项目总结/摘要 这项申请的广泛目标是建立一个跨非洲的神经精神遗传学计划， 确保神经精神病学的基因组学革命造福非洲的后代。很大的进步 在我们对精神分裂症遗传结构的理解中取得了重大进展。这些进步最终将 在减轻全球精神疾病负担方面发挥关键作用。然而，非洲人口 几乎没有神经精神遗传学研究，这对科学和医学都构成了挑战。 进步和全球公平。神经精神疾病遗传学研究中来自非洲人群的数据， 这对于生成遗传风险因素的完整图像并识别潜在缺失的新型治疗药物至关重要。 通过研究所有人群获得的信号。非洲人群中标记物之间的相关性降低 也可用于精细定位致病等位基因。除了发现，最近关于多基因风险评分的工作 显示了这些措施的临床应用潜力，但令人烦恼的是，交叉人群有限 可转移性和推广较差的性能在uncharacterized人群，如那些来自非洲。 神经精神遗传学的最新进展也有很大的风险，这将导致 非洲和世界其他地区之间巨大的研究和治疗差距。为了弥合这一差距， 我们与阿迪斯大学的同事合作，启动了NeuroGAP-精神病项目 埃塞俄比亚的Makerere大学、乌干达的Makerere大学和南非的开普敦大学， 建立一个多国神经精神遗传学研究和培训计划的伙伴关系， 哈佛T. H.陈氏公共卫生学院致力于实现以下具体目标：1）能力建设。 扩大非洲科学家进行精神分裂症和其他疾病大规模遗传研究的能力 能够在本地生成、分析和解释这些数据的精神障碍; 2）临床 特征化验证用于诊断和筛查精神分裂症和精神病的工具。系统地 描述13，000名精神分裂症和精神障碍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、物质使用和共病健康状况 条件; 3）基因发现。在非洲进行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， 精神分裂症在祖先相似的病例/对照人群。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”。我们 一个广泛的目标是制定一个可持续的研究和培训计划，旨在解决主要的限制 在我们的知识的遗传和环境风险架构的精神疾病的人， 非洲裔，并导致在非洲和所有人口的诊断，预防和治疗的改善。