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

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.