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 (Fig. 1(a)). 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 with 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 data-sets, as illustrated by the outputs from the global Psychiatric Genomics Consortium. Reference Agrawal, Bulik, Abebe, Andreassen, Atkinson and Choi2
Fig. 1 (a) Key genome-wide association studies for major depressive disorder from 2013 to 2025 (for references, see Supplementary File available at https://doi.org/10.1192/bjp.2026.10578), illustrating the number of cases with depression by genetic ancestry and the number of genome-wide significant loci identified. (b) Study centres for Depression Genetics in Africa, and 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, Reference Fatumo, Chikowore, Choudhury, Ayub, Martin and Kuchenbaecker3 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 (Fig. 1(a)). Although more recent studies have included diverse populations, including individuals of African ancestry, most are diaspora Africans in the Americas and Europe, enrolled in large-scale cohorts such as 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 generalisability of findings across populations, hindering both global insights into mental health disorders and their clinical translation into diverse settings.
Depression Genetics in Africa study
The Depression Genetics in Africa (DepGenAfrica) study was initiated to address the scarcity of continental African genetic data on MDD. Reference Okewole, Maina, Nakanga, Chebii, Smyth and Tholanah4 By expanding genetic data-sets, this initiative aims to enhance our understanding of the genetic architecture of MDD in Africa through coordinated collaboration among centres in Ethiopia, Malawi, Nigeria and South Africa (Fig. 1(b)).
Funded by Wellcome, the DepGenAfrica study brings together researchers from Africa (Ethiopia, Malawi, Nigeria, South Africa) and the UK (Fig. 1(b)). The project is funded from 2022 to 2027 and aims to recruit 12 000 participants (about half with MDD), with recruitment sites selected to capture genetic diversity across eastern, western and southern sub-Saharan Africa. Although not fully representative of all sub-Saharan populations, this strategy provides a pragmatic starting point, informed by existing collaborative research networks. This includes new participant recruitment in Ethiopia and Nigeria and leveraging 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. Reference Okewole, Maina, Nakanga, Chebii, Smyth and Tholanah4
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 the 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 standards
Ethics approvals were complex, because each institution followed its own procedures and African partners often required approval 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 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 those 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 the use of a well-validated electronic instrument for depression phenotyping in Africa based on established validation data and ease of administration (∼15 min 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. Reference Wing, Babor, Brugha, Burke, Cooper and Giel5
Questionnaire development and implementation in REDCap
The DepGenAfrica assessment tools are composed of multiple sections that require customised algorithms and branching logic, implemented in the REDCap software (v16.0.9, for Windows; Vanderbilt University, Nashville, Tennesee; https://projectredcap.org). This customisation, 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, because a finalised 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, because phenotyping and sample collection in Malawi are already under way, allowing us to build on existing efforts. However, certain differences in phenotyping across the sites present a challenge, because the assessments used for newly recruited participants will need to be harmonised with the existing data from Malawi. For instance, in Malawi, Patient Health Questionnaire 9 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 uploading 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, these 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 standardise 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
Whereas 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 −80°C 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. Below, we share our insights and offer recommendations to consider when planning similar projects in Africa.
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(a) Building trust and effective communication within the team: regular in-person meetings, particularly during the planning phase of multi-country projects, are vital. Although 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 multi-centre projects in Africa should allocate sufficient funding for at least two in-person meetings annually.
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(b) Project ethical and legal oversight: ethical science ensures that local communities are treated with respect and dignity, and can meaningfully understand the potential benefits from the research conducted in their communities. Multi-country 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 the 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.
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(c) Choosing and developing data collection tools: accurate and standardised 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 studies with established phenotyping protocols. Differences in cultural contexts and language must also be considered, because 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, prioritise validation efforts to maintain data integrity. Researchers should also consider cultural relevance, and methodological consistency when adapting or integrating existing data collection tools.
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(d) 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 −80°C 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 minimising disruptions. Recommendation: strengthening infrastructure in multi-country research projects requires early assessment of site needs and proactive collaboration. Leveraging expertise within the consortium can optimise resources, and cross-site knowledge-sharing enhances problem-solving. Establishing back-up storage solutions and alternative procurement strategies can further enhance sustainable research.
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(e) 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, standardised 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 standardised 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.
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(f) 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, ensuring responsible data-sharing while protecting the publication rights of investigators. Recommendation: governance frameworks should ensure fair authorship policies that recognise 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 is available online at https://doi.org/10.1192/bjp.2026.10578
Data availability
Data availability is not applicable to this article because no new data were created or analysed in this study.
Acknowledgements
We acknowledge all DepGenAfrica study members and study participants. We thank David Roberts for graphics design services.
Author contributions
J.G.M. was primarily responsible for manuscript drafting. A.O., B.M., N.S., J.W., A.C.C., T.L.S., S.T., M.R., G.B. and A.M. reviewed and edited the manuscript.
Funding
This work is funded by Wellcome grant nos 223165/Z/21/Z and 220857/Z/20/Z.
Declaration of interest
None.
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