Introduction

Mental health disorders have been one of the top ten causes of disease burden worldwide since 19901. In addition to the impact on individuals with a mental health disorder they have a wider impact on society. Individuals with mental health disorders can have severe distress and experience functional impairment in social and work environments2. Early life onset of mental health disorders has been strongly associated with truncated education attainment3. The prevalence of any mental health disorder is estimated at 12.3% globally and 13.4% in sub-Saharan Africa1.

Genetic research into psychiatric disorders has the potential to uncover mechanistic pathways underlying these disorders. These mechanistic pathways can be used to identify targets for drugs and to establish methods to screen new drugs. Recent genome-wide association studies have provided insights into the genetic architecture of several mental health conditions including major depressive disorder (MDD)4, suicidality5, post-traumatic stress disorder (PTSD)6 and schizophrenia7. However, these studies have been conducted largely among participants of European ancestry. The few participants of African ancestry that have been included have mostly been African Americans or people of African ancestry living in the United States and the United Kingdom, who may not be representative of the entire genetic diversity seen across Africa as populations which were not subject to forced migration are often not captured in such studies8,9.

Environmental factors also influence development of psychiatric disorders. There are substantial differences seen between the lived experience of people on the continent of Africa and elsewhere in the world. Thus, the full environmetal impact on development of psychiatric disorders can only be understood if studies are undertaken in Africa. It is also important to ensure people living in Africa can benefit from new treatments and diagnostic tools derived from these findings. There is a critical need to include continental Africans in global psychiatric genetic research, if they are to benefit from these discoveries.

This comment highlights the underrepresentation of African populations in psychiatric genetic research. It discusses challenges generally facing genetic research in Africa, such as unethical historical practices, immense cultural, language and genetic diversity and limited capacity and infrastructure. We also discuss strategies to facilitate undertaking of psychiatric genetic research in Africa (Fig. 1). It also showcases several African initiatives and efforts to improve representation of Africa, through establishing psychiatric genetic databases, community engagement and training programs such as the Global Initiative for Neuropsychiatric Genetics Education in Research program of Harvard and MIT (GINGER; https://ginger.sph.harvard.edu/). These collective efforts have the potential to advance psychiatric genetic research in Africa and ultimately make global psychiatric genetic research more equitable.

Fig. 1: Challenges and strategies for achieving equitable, inclusive and impactful psychiatric genetic research in Africa.
figure 1

The challenges (numbered) and proposed strategies could facilitate impactful psychiatric genetics research in Africa.

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Challenges

In the past, research in Africa was often conducted inappropriately10. There have been issues of ethical dumping, in which research studies and clinical trials have been conducted with less stringent ethical standards than those applied in developed countries. These practises included non-consensual testing and treatment, failing to fully explain studies and obtain proper informed consent, and exploitation of study participants. This led to partipants being unaware of the risk of participating or not being told, and hence being prevented from benefitting from the outcomes of the research. An example is the case where a United States drug manufacturer Pfizer was accused of testing a new drug (trovafloxacin) in Nigeria without ethical approval11. There have also been cases of parachute science, and exploitation where researchers from the developed world have conducted research in Africa without meaningful collaboration and involvement of local sccientists and communities. This approach has led to extraction of data from Africa with little or no benefit to Africa or its scientific community. For example, a systematic review of author affiliations for infectious disease research conducted in Africa between 1980 and 2016 reported underrepresentation of African researchers in the first and last authorship positions12. Such practices have resulted in mistrust issues, both among participants and the African researchers themselves, which has effected genetics research including psychiatric genetics.

The diversity within Africa extends beyond genetics to include ethnic and linguistic diversity, with over 3000 ethnic groups and 2000 languages spoken. This diversity offers a unique opportunity to understand human genetic evolution and the basis of disease but also poses challenges for genetic analysis due to the complexity of genetic variation. Language has been reported to impact population structure in Africa, independent of geography13. If not accounted for, differences in population structure can easily result in spurious genetic findings. Cultural and language differences can also significantly affect how research is conducted and how findings are communicated.

In addition, psychiatric genetic research in Africa has been limited by lack of funding and limited human and institutional capacity. There is a lack of the basic infrastructure for psychiatric genetic research, which is facilitated by advanced genetic research laboratories, biorepository services, reliable internet access and bioinformatics platforms. This problem is exacerbated by the expensive reagents and equipment needed for genetic research, such as large-scale sequencing or genotyping, which are usually more expensive to obtain in Africa than in many other countries. In addition there are a limited number of psychiatric genetic researchers in Africa. The lack of researchers in Africa with this expertise means there is less understanding of psychiatric and genetic concepts among African populations, which has further restricted research in Africa.

The few psychiatric genetics researchers in Africa can struggle to connect with their peers in the global north. This hinders their access to technology, funding and high-impact publication opportunities, which diminishes their global visibility. Limited networks also limit opportunities for mentorship, training and education for African scientists.

Even where data is available, genetic data from Africans has typically been excluded from large-scale genetic analyses focussed on samples of European ancestry. This exclusion is often justified by concerns about population stratification, which arise when two or more populations with different ancestries are analysed together, and until recently by the unavailability of transancestry methods9.

Strategies to overcome the challenges

To improve representation of Africa in psychiatric genetic research, African scientists are leveraging global collaboration to establish biobank initiatives for psychiatric genetic research in Africa. These initiatives are summarised in Table 1 and described here briefly. The National Institute of Mental Health (NIMH)-funded genomics of schizophrenia in the South African Xhosa people (SAX) study is investigating genetic risk for schizophrenia in 2200 South African Xhosa people (https://h3africa.org/index.php/consortium/the-genomics-of-schizophrenia-in-the-south-african-xhosa-people/). The Neuropsychiatric Genetics of African Populations – Psychosis (Neuro-GAP-Psychosis) study14 is funded by both the Stanley Center for Psychiatric Research and the NIMH, and has successfully recruited 43,100 participants (21,550 psychosis cases and 21,550 psychosis-free controls) from Uganda, Kenya, Ethiopia and South Africa, whose DNA has been sequenced by the blended-genome-exome (BGE) sequencing technology. The Wellcome trust funded DepGenAfrica study, seeks to recruit 12,000 participants from Ethiopia, Malawi and Nigeria to investigate the genetic risk for MDD. The Wellcome Trust funded GENDA study seeks to recruit 10,560 participants from the general population cohort in Uganda (https://www.lshtm.ac.uk/research/units/mrc-uganda/news/416321/ongoing-study-unit-presents-potential-discover-new-drugs-major-depressive-0) to assess MDD and sequence their DNA using BGE technology and ultimately combine data with other evolving datasets. In a parallel effort, the NIMH-funded GPA study (Genetics of PTSD in African Ancestry Populations: Enhancing discovery by addressing inequality) seeks to enhance PTSD genetics research by adding 16,000 new samples from Kenya and Uganda, integrating these with sequenced data from NeuroGAP-Psychosis as well as existing data on African diaspora participants from global biobanks and the psychiatric genomics consortium.

Table 1 Evolving and existing psychiatric genetic databases in Africa
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Enhancing community engagement and supporting ethical review mechanisms are essential for psychiatric genetic research in Africa and ensuring the success of these initiatives. Ethical issues in genetic research in Africa have been highlighted by members of many research ethics committees across Africa15. The need to strengthen ethical guidelines to reflect the evolving research landscape and boost awareness has also been highlited16. Such steps ensure that concerns and ethical issues related to data collection and use are adequately addressed, fostering trust among participants. African scientists also need to be fully involved in analysis and publication of their data. This has the potential to improve researcher—participant trust and understanding. Strengthening these areas helps navigate the complex ethical, legal, and social implications of psychiatric genetics, ensuring research integrity and participant protection while building capacity within health and research communities across the continent.

Technological advancements in genetic analysis, such as CT-SLEB (a software program which calculates polygenic risk scores based on ancestry-specific genome-wide association study summary statistics from multiancestry samples) and PRSCSx (a software program which calculates polygenic risk scores based on continuous shrinkage priors) offer improved handling of multi-ancestry data, which should enable African ancestry data to be better integrated into global psychiatric genetic research17,18. However, there is need to generate psychiatric genetic data to be available for analysis when the right tools become available. Additionally, capacity needs to be built for the use of new tools and publication of research papers from Africa. African scientists need to be prepared to lead in the analysis of their data. This is linked to another important consideration, the importance of engaging clinicians, stakeholders and the public in psychiatric genetic research and encouraging its application in mental health services.

Addressing the critical need for skilled genetic researchers in Africa requires substantial training and infrastructure development. Initiatives such as the GINGER fellowship program and the work of the African Society of Human Genetics exemplify successful capacity-building efforts. For example, one of the authors, Allan Kalungi, a GINGER fellow, is now advancing depression genetics research in Africa post-fellowship. The Mental Health Data prize Africa, initiated by the African Population and Health Research Center (APHRC) in partnership with the Wellcome trust complements these efforts (https://mentalhealthdataprizeafrica.aphrc.org). This initiative has over a five months period trained early and mid-career researchers from Africa in advanced statistical analysis and machine learning algorithms tailored for mental health applications in Africa. Additionally, this initiative has advertised a funding scheme which aims to give out about five to ten 1 year research awards, each valued at £200,000. For these awards, multidisciplinary teams will have opportunity to team up and generate scalable inovations and data driven insights into anxiety, depression and psychosis in Africa (https://www.mentalhealthdataprizeafrica.aphrc.org/new-initiative-to-boost-mental-health-research-in-africa.html). Furthermore, the establishment of Centers of Excellence in Bioinformatics in Uganda and Mali, through collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and local entities (https://ace.niaid.nih.gov/about) are making progress in creating a robust infrastructure for psychiatric genetic research in Africa. These centers, alongside other high-performance computing facilities across the continent, are essential for analysing and storing large-scale genetic data, which will advance Africa’s genetic research capability.

Funders must initiate psychiatric genetic funding schemes which specifically target researchers in Africa to address the previous lack of funding and enhance diversity. Collaborations within Africa are also essential for sharing resources among researchers with similar psychiatric genetic interests, and have led to the formation of the Psychiatric Genomics Consortium Africa (https://pgc.unc.edu/for-researchers/diversity-working-groups/afr/#:~:text=The%20Africa%20Working%20Group%20of,Africans%20working%20in%20the%20diaspora). This provides an opportunity to harmonise phenotype definition and analysis methods, to allow easier aggregation of data.

Genetic analysis methods among Africa’s diverse populations must address population stratification and should be optimised for the continent’s genetic variability. For instance, research conducted among participants from Uganda recommended that a genome-wide association study (GWAS) statistical threshold of 5.0 × 10-9 is relevant in populations with high genetic diversity and relatively lower levels of linkage disequilibrium patterns as opposed to the commonly considered threshold of 5.0 × 10-8 19. Informed consent in studies conducted in such communities should be administered in a manner that is culturally sensitive and understandable to the research participants. Care should also be taken when reporting back research findings. For example, identification of genetic variants associated with particular diseases in specific ethnic groups may lead to stigmatisation.

There is need for collaborations between psychiatric genetic researchers based in Africa and researchers from the global north. These collaborations are vital for sharing expertise, enhancing grant competitiveness, and accessing advanced technologies. Such partnerships should prioritise equity, with African scientists leading research agendas and publications. The Human Heredity and Health in Africa (H3Africa) consortium exemplifies a successful model to foster genetic research in Africa in which African researchers play a central role (https://h3africa.org).

Concluding remarks

Several strategies need to be undertaken to mitigate challenges that hinder psychiatric genetic research in Africa. For example, there is need for development and implementation of trans-ancestry methods as well as the need to; increase public awareness about the importance of psychiatric genetic research in Africa, advocate for policies which prioritise mental health and psychiatric genetic research, develop and maintain biobanks with well annotated biological samples, establish more equitable international partnerships and consortia involving African scientists and institutions, among others. In conclusion, advancing psychiatric genetic research in Africa requires a number of issues which must be addressed and it will take robust investment, inclusive engagement and collaborations, as well as culturally sensitive methodologies to unlock the continent’s vast genetic potential, for the well-being of the people therein.