Advancing neuropsychiatric genetics training and collaboration in Africa

Merwe, Celia van der; Mwesiga, Emmanuel Kiiza; McGregor, Nathaniel W.; Ejigu, Abebe; A, Tilahun; Kalungi, Allan; Akimana, Benedict; Dubale, Benyam Worku; Omari, Felicita; Mmochi, Jackline; Majara, Lerato; Ongeri, Linnet; Alemayehu, Melkam; Koen, Nastassja; Dalvie, Shareefa; Kariuki, Symon M.; Hoogenhout, Michelle

doi:10.1016/s2214-109x(18)30042-1

Cited by 9 publications

(9 citation statements)

References 11 publications

(8 reference statements)

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“…The exclusion of African researchers leads to the disparity in research leadership and reduced scientific output from African researchers (Bentley et al, 2020) . Efforts such as the NeuroGAP Global Initiative for Neuropsychiatric Genetics Education and Research (GINGER) program (van der Merwe et al, 2018) , which provides mentorship and training for early-career investigators on the African continent (particularly in Uganda, Kenya, Ethiopia and South Africa, including several of this study's authors), are important in moving toward a more inclusive and representative research community.…”

Section: Discussionmentioning

confidence: 99%

Low generalizability of polygenic scores in African populations due to genetic and environmental diversity

Majara

Kalungi

Koen

et al. 2021

Preprint

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African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRS) in simulations across Africa and in empirical data from South Africa, Uganda, and the UK to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South Africans, we find that PRS accuracy is low for all traits but varies across groups. Differences in African ancestries contribute more to variability in PRS accuracy than other large cohort differences considered between individuals in the UK versus Uganda. We computed PRS in African ancestry populations using existing European-only versus ancestrally diverse genetic studies; the increased diversity produced the largest accuracy gains for hemoglobin concentration and white blood cell count, reflecting large-effect ancestry-enriched variants in genes known to influence sickle cell anemia and the allergic response, respectively. Differences in PRS accuracy across African ancestries originating from diverse regions are as large as across out-of-Africa continental ancestries, requiring commensurate nuance.

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Section: Discussionmentioning

confidence: 99%

Low generalizability of polygenic scores in African populations due to genetic and environmental diversity

Majara

Kalungi

Koen

et al. 2021

Preprint

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“…To help ensure all collaborators have the capacity to work with all the data that will be created, a unique training programme has been created, the Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER),41 that will run in parallel to the NeuroGAP-Psychosis study. Over a 2-year period, 17 early-career researchers from Ethiopia, Kenya, South Africa and Uganda will take part in online and in-person trainings on topics including biostatistics, genetic analysis and epidemiology.…”

Section: Methods and Analysismentioning

confidence: 99%

Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda

et al. 2019

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IntroductionSchizophrenia and bipolar disorder account for a large proportion of the global burden of disease. Despite their enormous impact, little is known about their pathophysiology. Given the high heritability of schizophrenia and bipolar disorder, unbiased genetic studies offer the opportunity to gain insight into their neurobiology. However, advances in understanding the genetic architecture of schizophrenia and bipolar disorder have been based almost exclusively on subjects of Northern European ancestry. The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project aims to expand our understanding of the causes of schizophrenia and bipolar disorder through large-scale sample collection and analyses in understudied African populations.Methods and analysisNeuroGAP-Psychosis is a case-control study of 34 000 participants recruited across multiple sites within Ethiopia, Kenya, South Africa and Uganda. Participants will include individuals who are at least 18 years old with a clinical diagnosis of schizophrenia or bipolar disorder (‘psychosis’) or those with no history of psychosis. Research assistants will collect phenotype data and saliva for DNA extraction. Data on mental disorders, history of physical health problems, substance use and history of past traumatic events will be collected from all participants.DNA extraction will take place in-country, with genotyping performed at the Broad Institute. The primary analyses will include identifying major groups of participants with similar ancestry using the computation-efficient programme single nucleotide polymorphisms (SNP) weights. This will be followed by a GWAS within and across ancestry groups.Ethics and disseminationAll participants will be assessed for capacity to consent using the University of California, San Diego Brief Assessment of Capacity to Consent. Those demonstrating capacity to consent will be required to provide informed consent. Ethical clearances to conduct this study have been obtained from all participating sites. Findings from this study will be disseminated in publications and shared with controlled access public databases, such as the database of Genotypes and Phenotypes, dbGaP.

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“…83 NeuroGAP has also established the Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER), which will support the training of early-career investigators from the countries in which research is being conducted (Ethiopia, Kenya, South Africa, and Uganda). 84 The topics for training are determined through the participation of the fellows and their African mentors, so that their needs shape their experiences. 84 H3Africa supports the development of large collaborations across multiple centers, leverages synergies between studies, and provides critical training to African researchers.…”

Section: Infrastructure To Include Diverse Voicesmentioning

confidence: 99%

“…84 The topics for training are determined through the participation of the fellows and their African mentors, so that their needs shape their experiences. 84 H3Africa supports the development of large collaborations across multiple centers, leverages synergies between studies, and provides critical training to African researchers. The pan-African bioinformatics network, H3ABioNet, was designed to serve the consortium and assists with data quality control and analysis.…”

Section: Infrastructure To Include Diverse Voicesmentioning

confidence: 99%

Evaluating the promise of inclusion of African ancestry populations in genomics

2020

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The lack of representation of diverse ancestral backgrounds in genomic research is well-known, and the resultant scientific and ethical limitations are becoming increasingly appreciated. The paucity of data on individuals with African ancestry is especially noteworthy as Africa is the birthplace of modern humans and harbors the greatest genetic diversity. It is expected that greater representation of those with African ancestry in genomic research will bring novel insights into human biology, and lead to improvements in clinical care and improved understanding of health disparities. Now that major efforts have been undertaken to address this failing, is there evidence of these anticipated advances? Here, we evaluate the promise of including diverse individuals in genomic research in the context of recent literature on individuals of African ancestry. In addition, we discuss progress and achievements on related technological challenges and diversity among scientists conducting genomic research.

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Advancing neuropsychiatric genetics training and collaboration in Africa

Cited by 9 publications

References 11 publications

Low generalizability of polygenic scores in African populations due to genetic and environmental diversity

Low generalizability of polygenic scores in African populations due to genetic and environmental diversity

Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda

Evaluating the promise of inclusion of African ancestry populations in genomics

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