In 2020, an analysis of 426 African genomes, involving researchers from 15 African countries, uncovered 3 million new variants in the human genome. The discovery contributed to the development of a tool enabling researchers to identify genetic associations, specifically in African populations – the Infinium H3Africa Consortium genotyping array, produced by the United States (US) biotechnology firm Illumina.
Although various enterprises have supported cutting-edge human genomics in Africa, the Human Heredity and Health in Africa (H3Africa) initiative, which supported this work, has probably contributed the most, (but running out this year), was funded by the US National Institutes of Health (NIH) and the United Kingdom biomedical charity, Wellcome, in partnership with the African Society of Human Genetics. Projects have ranged from population-based genomic studies of common disorders, such as heart disease, to investigations of infectious diseases, such as COVID-19. Altogether 51 projects led by African scientists and involving researchers from more than 30 African countries, have resulted in 50,000 samples being genotyped and nearly 700 papers being published.
Thanks to H3Africa and other genomics initiatives, such as the Nigerian 100K Genome Project3, African genomics is now poised to improve the health of those findings to clinics. This will however require several systemic changes a major shift in how genomics on the continent is funded.
All remaining projects supported by the H3Africa initiative are expected to wrap up this year. An in-depth article in Nature, a global scientific publication, laid out what is needed to ensure investment in Africa genomics to be sustained in a post-H3Africa world, expanded for Africa to become the birthplace for a new kind of genomics, bringing better health to all.
H3Africa’s Achievements by Addressing Inequity
As of 2021, nearly 86% of participants in genome-wide association studies (GWAS) worldwide were of European descent, even though that group makes up only 16% of the world’s population. This bias means that precision-medicine tools, such as polygenic risk scores, using genetic data to predict a person’s risk of developing a certain disease, are much more accurate for people of European ancestry.
H3Africa has made it easier for Africans to pursue genomics on the continent by establishing sequencing facilities, in South Africa, Gambia, Nigeria, Ethiopia, Uganda and Botswana. Training programmes were launched in bioinformatics. African institutions were direct recipients of grants in the H3Africa programme, enabling Africans to design projects, develop training programmes and establish infrastructure according to the needs of their respective countries.
Also, H3Africa has increased the profile of African genomics globally, thanks to researchers and organisations funded by H3Africa, partnering with international bodies, such as the Heads of International Research Organizations (HIRO), the National Institute for Health in the United Kingdom and the Bill and Melinda Gates Foundation.
H3Africa has grown genomics education and awareness across the continent by requiring that all projects include some amount of community engagement. For example, Genome Adventures, an initiative of an H3Africa-funded network of organisations, the Collaborative African Genomics Network, is likely to have contributed to the high retention rate of participants in the network’s research project. In this case, workshops, comic books and social media were used to educate community stakeholders and the public about genomics and biomedical research.
Furthermore, H3Africa has enabled an unprecedented degree of scientific collaboration between researchers, both across the continent and elsewhere, requiring that funded African researchers collaborate with other African scientists. During the COVID-19 pandemic, for example, researchers at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID) in Ede, Nigeria, trained more than 1,300 geneticists, public-health workers and officials from other African countries in diagnostics, next-generation sequencing and bioinformatics.
Lastly, by providing ethics guidelines tailored to African settings, H3Africa has assisted in establishing standards and norms around data sharing and communication of findings to study participants. Although the rules and regulations on this vary greatly across Africa’s 54 countries, geneticists across the continent now have a central resource for guidance on informed consent, stigma around genetic diseases and the sharing of benefits from studies and other topics.
Realistic Goals and Real-World Impact
Although most H3Africa projects have not yet translated findings into clinical practice, some have already had real-world impact. For instance, over the past eight years, work at ACEGID has shared public-health responses to Lassa fever, Ebola and COVID-19. Likewise, to improve paediatric care, Solomon Ofori-Acquah, an H3Africa-funded researcher at the University of Pittsburgh in Pennsylvania and at the University of Ghana in Accra, last year established a genetic screening programme for new-borns in Ghana which was paired with a genetic-counselling training programme.
But will all this progress in African genomics be sustained after H3Africa funding ends? What is needed to ensure that current and future investments translate into improved health for people?
The Collaborative African Genomics Network, part of the H3Africa consortium, produced a set of four Genome Adventures comic books to improve public understanding of genomics in Botswana. Building a continent-wide early-warning system to detect and track disease outbreaks could be achieved through scaling up the ACEGID model. Such centres across Africa would enable training of its scientists, help to retain African talent and ensure standards of practice around African genomic surveillance are developed on the continent itself. The Africa Centres for Disease Control and Prevention have already established a surveillance network – the Pathogen Genomics Initiative. This consists of national public health institutes and genomics laboratories, such as ACEGID.
In other areas, health benefits are still further in the future. This include treatment of common, non-infectious conditions (such as diabetes), largely because of a lack of data and the treatment of rare diseases, largely because of a lack of genomic medicine services.
Because African genomes have a longer evolutionary history and harbour more variation than genomes of people with European ancestry, they offer a richer source of variants linked to traits of interest, such as rare developmental disorders. Studies are revealing the incredible potential of African genomes for developing ways to diagnose diseases across diverse populations, uncovering new therapeutic targets and identifying genetic markers able to indicate how someone might respond to a particular drug.
As an example, throughout the world, a mutation in a gene on chromosome 4 is used to diagnose Huntington’s disease. However, another form of the disease exists that is clinically indistinguishable, called Huntington’s disease-like 2 (HDL2). This is caused by a mutation in a gene on chromosome 168,9. So far, all cases of HDL2 have been found in people with African ancestry, suggesting that individuals showing Huntington’s disease symptoms but do not have the chromosome 4 mutation, should be tested for the mutation on chromosome 16.
To deliver the greatest yield per investment towards translatable findings in African genomes, a network of genomic centres needs to be established across Africa. Geneticists operating in such a network should collaborate with those working on multi-year cohort studies to find the effects of genetic and environmental factors, particularly for complex diseases.
One encouraging sign is a funding award to aid in establishing the African Population Cohort Consortium. Last year, the African Population and Health Research Centre in Nairobi received funding from Wellcome to develop and co-lead this consortium with the Africa Health Research Institute in Durban, South Africa. It will collate health-surveillance data and bio-specimens to provide a resource for large-scale population studies.
Ideally, investment in an African genome initiative at scale should occur alongside the establishment of a pan-African biobank similar to the UK Biobank, which periodically collects health and genetic information from more than 500,000 participants since 2006. H3Africa has already established bio-repositories in Uganda, Nigeria and South Africa, involved in the collection of samples linked to the H3Africa genetic data resource. The Genetics of Latin American Diversity (GLAD) Project, which includes genome-wide data on 54,000 individuals from 39 studies, shows that such a standardised, pan-continental approach is feasible.
The Changes Needed
In July last year, the World Health Organization’s (WHO) Science Council, which advises the WHO director-general on high-priority scientific issues, stressed the importance of genomics to future global health in a special report by calling for and realising the goals laid requiring four systemic changes to genomics research in Africa.
African governments have been slow to support genomics infrastructure. None of them has delivered on pledges made at the 2007 African Union assembly to spend 1% of gross domestic product on research and development by 2010.
In the Nature article, authors said that convincing political leaders in Africa to invest in genomics has been challenging as it can take decades before pay-offs. The fact that most evidence for the benefits of genomics comes from research on European-ancestry populations in high-income settings also makes it harder for scientists to convince African governments that genomics could help their own people.
However, as long as researchers rely on grants from outside funders such as the NIH, African governments will not have ownership of projects or be able to set priorities. Also, sustained government commitment to genomics, which would enable researchers and health-care practitioners to keep working in Africa, is crucial to bringing genomic medicine benefits to local populations.
Matched funding schemes, whereby funds are provided by a donor on the condition that the receiver (the country) also contributes resources could help to shift trends in Africa away from over-reliance on donor ship.
South Africa houses around one-quarter of all next-generation sequencing facilities on the continent. For genomic medicine to have an impact on the health of millions, data of similar quality to those used in the global north need to be generated and should be produced at a similar pace and price.
More government investment would help with this. Public–private partnerships are also key factors to success. Major pharmaceutical companies are increasingly expressing interest in scaling up translational genomics in Africa. At the American Society of Human Genetics annual meeting last October, an emerging consortium of seven firms met with H3Africa investigators to discuss how current fragmented initiatives might be transformed into an integrated public–private partnership.
The responsible engagement of industry, based on principles of African ownership and the equitable distribution of credit and benefits, will go a long way towards addressing crucial needs, such as lack of maintenance staff for sequencing machines, affordable reagents and reliable supply chains.
Various endeavours have already demonstrated the promise of public–private partnerships. For instance, a genomics centre was established in 2018 in Cape Town, South Africa, thanks to a partnership between the Chinese genomics company BGI Group and the South African Medical Research Council. It was one of the facilities used to detect Omicron SARS-CoV-2 variants in South Africa’s wastewater by using high-throughput sequencing.
Similarly, in 2021, the Illumina and Genetic Alliance, a non-profit organisation supporting research on rare diseases, launched the iHope Genetic Health programme. This $120-million initiative aims to expand global access to whole-genome sequencing, with more than one-third of the money awarded to Africa.
Genetic Services and Electronic Health Recording
In the United States, there are 2 medical geneticists and 7 genetic counsellors for every 500,000 people. In South Africa, which offers the most extensive medical genetics services in Africa, both these numbers are less than 0.2
For people in Africa to benefit from potentially transformative genomic medicine applications, such as emerging gene-based therapies for sickle-cell disease, genetic counselling services are needed in every country. Even with limited screening, sickle-cell disease is known to affect around 225,000 babies in Africa annually. It is estimated that the disease results in 8–15 deaths per 1,000 children under 5 years old on the African continent. Electronic health-record systems are essential if the use of genomic information in clinical care is to become routine.
Equitable Science and Meaningful Engagement among Research Participants
The legacies of colonialism and scientific racism continue to block opportunities for African scientists to participate equitably in genomics.. Research focusing on diseases most prevalent in Africa, are often led by non-African organisations. Researchers globally have frequently failed to consider how benefits stemming from their work could be shared equitably and some genome data have been used unethically.
Changing this will require a commitment from all stakeholders to promote equitable collaboration with partners in Africa, modelled on the successes of programmes such as H3Africa. A broader array of funders, including major philanthropic organisations, needs to support genomics initiatives on the continent. Priority should be given to proposals for projects led by African scientists, representing African populations and specifically those focusing on research questions pertinent to African communities.
To ensure that research is shaped according to the priorities of people living in Africa, engagement with research participants must also be tailored to specific cultures and languages. Some 2,000 languages are spoken in Africa, representing a significant barrier to communication. The Lyfe Languages initiative, a project developed in Western Australia to help overcome a barrier between Aboriginal people and health-care providers, offers one model for how this might be achieved. The project provides indigenous language of terms often used in clinical-genetics research.
The next decade
Researchers who have dependent on H3Africa funds are in a strong position to compete for the global money pot available for genomics research. This includes grants offered by the NIH and the US National Science Foundation. Many have been awarded grants to join a new consortium called Data Science for Health Discovery and Innovation in Africa (DS-I Africa). This effort, which is focused on data science and analysis, builds on H3ABioNet, H3Africa’s bioinformatics training programme and is funded for up to ten years by the NIH Common Fund Initiative.
Most researchers urgently need African governments and other funders to step up to help them secure a viable research future on the continent. Governmental commitment is crucial to securing a sustainable future for personalised medicine and medical genetics services across African countries.
A group of H3Africa investigators and NIH colleagues are proposing a programme of Genomics Centres of Excellence. These could absorb multiple genomics projects, scale up training, adopt common standards and, through institutional strengthening, offer greater sustainability than sponsorship of individual projects alone.
An incredible amount has been achieved in little more than ten years. But with the right investment from the right stakeholders, Africa could achieve so much more in genomics in the decade ahead, with benefits that reach far beyond the continent.