Psychiatric Genetics Research in Africa: Challenges, Opportunities and Strategic Insights from the Depression Genetics in Africa (DepGenAfrica) study

Abstract

The Depression Genetics in Africa (DepGenAfrica) study addresses underrepresentation of African populations in psychiatric genomics by investigating the genetic basis of major depressive disorder in Ethiopia, Malawi, and Nigeria. This Editorial reflects on lessons from project set-up and offers recommendations, highlighting trust, communication, ethical oversight, data tools, workforce training, and resource governance.

Overview of global psychiatric genetics

As the sample sizes and ancestral diversity for genomic studies increase, so do the number of genetic variants associated with the phenotypic outcome. This holds true for psychiatric disorders where the latest genome-wide association study (GWAS) for major depression including nearly 700,000 cases, with 23% in non-European ancestries, identified 635 genome-wide significant loci (Figure 1A). The increased power associated with such large GWAS sample sizes provides data for downstream studies leading to improved risk prediction and the ability to determine stronger causal inferences. Notably, the proportion of liability variance explained by polygenic scores among European ancestry improved to 5.8% compared to 3.2% in a previous study (1). Collaboration is a key driver of progress in global psychiatric genetics, allowing for the analysis of larger and more genetically diverse datasets, as illustrated by the outputs from the global Psychiatric Genomics Consortium (PGC) (2).

Figure 1.

Panel A. Key genome-wide association studies (GWAS) for Major Depressive Disorder (MDD) from 2013 to 2025 (references in Supplementary File) illustrate the number of cases with depression by genetic ancestry and the number of genome-wide significant loci identified. Panel B. Study sites for DepGenAfrica and the overview of the collaborative structure between UK and African partner institutions

Limitations of current psychiatric genetics studies

Despite significant breakthroughs in psychiatric genetics, current research still falls short of global representation. The underrepresentation of non-European ancestry study participants in GWAS (3), especially from cohorts resident in Africa, extends to studies of the genetics of major depressive disorder (MDD). Over the past decade, most GWAS of MDD have been conducted exclusively in individuals of European ancestry (Figure 1A). Although more recent studies have increasingly included diverse populations, including individuals of African ancestry, most are diaspora Africans in the Americas and Europe, enrolled in large-scale cohorts like the Million Veteran Program, All of Us Research Program, and UK Biobank. However, diaspora Africans do not fully capture the genetic diversity or environmental context of the African continent. Most originate from the Niger-Congo ethnolinguistic group, one of Africa’s five major genetic lineages. This lack of ancestral diversity in psychiatric genetics limits the generalizability of findings across populations, hindering both global insights into mental health disorders and their clinical translation into diverse settings.

Depression Genetics in Africa (DepGenAfrica)

DepGenAfrica was initiated to address the scarcity of continental African genetic data on MDD(4). By expanding genetic datasets, this initiative aims to enhance our understanding of the genetic architecture of MDD in Africa through coordinated collaboration among participating centres in Ethiopia, Malawi, Nigeria and South Africa (Figure 1B).

Funded by Wellcome, the DepGenAfrica study brings together researchers from Africa (Ethiopia, Malawi, Nigeria, South Africa) and the United Kingdom (Figure 1B). The project is funded between 2022 and 2027 and aims to recruit 12,000 participants (about half with MDD), with sites selected to capture genetic diversity across sub-Saharan Africa spanning eastern, western and southern African regions, through new recruitment in Ethiopia and Nigeria, and existing population studies in Malawi. Genetic data generation (array genotyping and/or sequencing) will be coordinated through the Sydney Brenner Institute for Molecular Bioscience in South Africa, given its established expertise and infrastructure for large-scale genomic research. A wide range of phenotypes will also be collected as described elsewhere (4).

As recruitment progresses in Ethiopia and Nigeria, we reflect on the journey that brought us to this stage, along with the challenges, opportunities, and strategic insights shaping such psychiatric genetic studies in Africa.

Challenges

Executing a new psychiatric genetics data collection project is a complex and demanding endeavour, requiring careful planning and perseverance. Despite significant progress in the DepGenAfrica journey, we have identified key challenges that have delayed the implementation of this large-scale, multi-country genetic study in Africa by nearly 2 years in some sites.

Ethical and legal compliance

Ethics approvals were complex, as each institution followed its own procedures, and African partners often required approvals from both local and UK collaborators. Limited ethics committee capacity and experience with multi-country genetic studies contributed to delays, especially in settings where reviewer participation is voluntary, the review process is multi-staged and ethics committee meetings are scheduled irregularly. Material transfer agreements (MTAs) and import/export permits were required to transport samples across borders and had to be legally compliant with multiple national laws, which could take weeks or months to finalise. Compliance with data protection laws and laws governing the banking of biological materials (either in country or across national borders) differed across countries meaning that we had to be adaptable and creative in processing genetic data.

Costs of screening tools

DepGenAfrica initially proposed using a well-validated electronic instrument for depression phenotyping in Africa based on established validation data and ease of administration (~15 minutes per participant). However, due to its high cost and the lack of any available discounts to African nations based on bulk administration, we opted for a freely available instrument that we could adapt for our unique setting - the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) tool (5).

Questionnaire development and implementation in REDCap

The DepGenAfrica assessment tools are composed of multiple sections that require customized algorithms and branching logic, implemented in the REDCap software (v16.0.9 on Windows, Vanderbilt University, projectredcap.org). This customization coupled with the need to reach agreement on which items to include and how to integrate country-specific elements, presented unanticipated challenges. Collectively, these delays also indirectly impacted the ethics application process, as a finalized version of the questionnaire is required for ethical approval.

Complexities of onboarding existing studies

DepGenAfrica will recruit new participants in Ethiopia and Nigeria while identifying cases and controls from ongoing population studies in Malawi; Generation Malawi and Healthy Lives Malawi. This represents an early success for the project, as phenotyping and sample collection in Malawi are already underway, allowing us to build on existing efforts. However, some differences in phenotyping across the sites present a challenge, as the assessments used for newly recruited participants will need to be harmonised with the existing data from Malawi. For instance, in Malawi, the PHQ-9 questionnaire is the primary depression phenotyping tool, whereas in Ethiopia and Nigeria depression is primarily assessed using the SCAN questionnaire.

Operational and logistical challenges

The clinical and organisational commitments of investigators within DepGenAfrica often limited their availability for scheduled calls, occasionally delaying critical decision-making. Additionally, connectivity issues, such as internet disruptions and power outages, frequently hindered smooth meeting coordination, and upload of data from the data capture devices. Beyond communication barriers, logistical challenges also emerged. In Nigeria, the initial proposal included 22 recruitment sites, but on careful review of the required logistics and high cost for each additional site, they were reduced to 2. The sourcing and shipping of essential project materials, including sample collection kits, reagents, and measuring instruments has also been a key challenge. In some countries suppliers could not be identified for specific reagents and kits, making it difficult to standardize procedures across sites.

Cross-cultural differences

Africa’s diversity is reflected in both its genetics and cultures, requiring careful consideration when implementing and conducting multi-country studies. Obtaining consent often involves navigating complex local dynamics, and questionnaires must be adapted to reflect population-specific sensitivities. For example, questions related to cognition, intimate partner violence, consanguinity, or parental ethnicity may be particularly sensitive in some communities.

Infrastructure

While recruitment in Ethiopia and Nigeria leveraged existing hospital settings, laboratory capacity for sample storage and processing varied across sites. Some locations faced challenges such as limited access to -80ºC freezers, impacting their ability to store biosamples on-site. The establishment of in-country sample processing not only facilitates the current study but also lays the groundwork for local biobanks, creating valuable resources for future research and potential investment in genetic studies. Access to DNA genotyping and sequencing also varied across participating countries and therefore all genetic data generation will be coordinated centrally from South Africa.

Training

Training psychiatrists, research assistants, and laboratory staff for DepGenAfrica presented significant challenges. Coordinating psychiatrists was particularly difficult due to their varying clinical schedules, especially in sites where recruitment centres were geographically dispersed. This was further complicated by the limited availability of qualified trainers for the SCAN questionnaire, as well as the need to adapt it to regional contexts. Extensive training of all staff was conducted at each site, including reliability assessments, and further refresher training will be provided in future.

Strategic insights and recommendations

Overcoming the challenges has made the DepGenAfrica team more aware of the issues involved in conducting genetic studies in Africa, and has built relationships within and outside the consortium as members navigated these obstacles and built trust. We share our insights and offer recommendations to consider when planning similar projects in Africa.

1. Building trust and effective communication within the team: Regular in-person meetings, particularly during the planning phase of multi-country projects are vital. While virtual meetings are cost-effective, the significant progress that was achieved in face-to-face discussions more than justifies the additional investment. These meetings played a crucial role in accelerating consensus on key issues such as questionnaire design, authorship guidelines, and the adaptation of phenotyping tools. Recommendation: Researchers preparing grants for multicentre projects in Africa should allocate sufficient funding for at least two in-person meetings annually.

2. Project ethical and legal oversight: Ethical science ensures that local communities are treated with respect and dignity, and can meaningfully understand potential benefits from the research conducted in their communities. Multicountry genetic projects in Africa face unique challenges related to ethics approvals and legal compliance. In DepGenAfrica, having expertise and experience with the ethical issues related to genomic research in Africa has been invaluable to ensure that the specific requirements and constraints imposed by ethical review boards across study sites could be thoroughly addressed and respected, including community sensitisation and engagement. Recommendation: Begin the ethical approval processes early and develop a clear understanding of the regulatory and ethical frameworks of each participating institution and country. Allocate sufficient time for approvals and engage an ethics expert familiar with the complexities of African genomics research to help guide the process effectively.

3. Choosing and developing data collection tools: Accurate and standardized phenotyping across study sites is essential for drawing reliable genetic inferences in psychiatric research. However, achieving consistency can be challenging, particularly when identifying cases and controls from ongoing study with established phenotyping protocols. Differences in cultural contexts and language must also be considered, as some tools may lack sufficient sensitivity to capture certain culturally relevant aspects of mental health. Additionally, adapting instruments, such as incorporating context-specific examples or modifying questionnaire length, requires careful evaluation to maintain validity and comparability across sites. Recommendation: Engage in consensus-building early to ensure alignment on phenotyping tools across study sites. Where modifications are necessary, prioritize validation efforts to maintain data integrity. Researchers should also consider cultural relevance, and methodological consistency when adapting or integrating existing data collection tools.

4. Assessing and developing essential infrastructure: Infrastructural limitations were addressed in DepGenAfrica through strategic collaborations, where institutions with greater resources support capacity-building efforts across the partner institutions. For example, UK and South African partners have facilitated resource-sharing, supporting other African partner institutions in acquiring essential equipment such as sphygmomanometers and -80ºC freezers, and providing training opportunities for early-career researchers to strengthen technical expertise. Additionally, collaboration between African partner institutions has been instrumental in overcoming logistical challenges. By sharing experiences in procuring materials and reagents for sample processing, institutions have identified efficient procurement pathways, ensuring timely delivery and minimizing disruptions. Recommendation: Strengthening infrastructure in multicountry research projects requires early assessment of site needs and proactive collaboration. Leveraging expertise within the consortium can optimize resources, while cross-site knowledge sharing enhances problem-solving. Establishing backup storage solutions and alternative procurement strategies can further enhance sustainable research.

5. Workforce training: Training clinicians, research assistants and laboratory staff involved in participant recruitment and sample processing is essential for the successful implementation of genetic studies. To ensure consistency in data and sample collection across sites, standardized training protocols should be adopted. A practical approach is the implementation of joint training sessions for trainers from each site, who then cascade the information within their recruitment centres. This process highlighted potential cultural and population-specific factors that had to be considered, improving study implementation. Recommendation: Develop standardized training protocols and conduct joint training sessions early to ensure alignment across study sites. To enhance feasibility and data quality, incorporate site-specific considerations into training and implementation.

6. Data and resource governance: Clear policies on data ownership, sharing, and decision-making are essential for maintaining transparency and fairness in collaborative research. In DepGenAfrica, data access is managed through a controlled access model under the Data Access Committee (DAC), ensuring responsible data sharing while protecting the publication rights of investigators. Recommendation: Governance frameworks should ensure fair authorship policies that recognize the contributions of all researchers. Data-sharing agreements should also support institutional capacity building and align with national research priorities and legal frameworks.

Conducting psychiatric genetics research in Africa presents unique and complex challenges, many of which can be effectively addressed. This document provides valuable insights into navigating these complexities. Expanding studies on African populations is essential for a more comprehensive understanding of illnesses affecting people worldwide. DepGenAfrica is a landmark study tackling a significant gap in global psychiatric genetics, bringing us one step closer to understanding MDD. We hope that this report will help streamline processes and accelerate the delivery of future projects.

Supplementary Material

The supplementary material for this article can be found at https://docs.google.com/document/d/1akPs7WGiAGr4YM8aOBlWaxtCqswIcY-N2IUy0EwU6Fo/edit?usp=sharing

Data availability

Data availability is not applicable to this article as no new data were created or analysed in this study.