It is no secret that modern humans originated in Africa. According to a 2009 study, still considered the most comprehensive study of African genetic diversity to date, Africa was revealed to be the most genetically diverse continent on Earth. Due to their complex population history and the dramatic variation in climate, diet, and exposure to infectious disease, African descendants have higher levels of genetic and phenotypic variation than counterparts from other ancestries. That wealth of genetic variation therefore makes them an important source of global genomics research.
Yet, their genes are highly underrepresented in genomics research. For decades, Genomic Wide Association Studies have been based on analysis of datasets almost exclusively representing individuals of European ancestries (78 per cent). As such, all other groups are underrepresented in those datasets, including African ancestry populations. This means disease risk prediction in African descendants has mostly used data from European ancestry populations. Needless to say this has not led to reliable or conclusive results.
Underrepresentation at the cost of precision medicine
The UK biobank, one of the world’s largest “biomedical databases and research resources, containing in-depth genetic and health information from half a million UK participants,” is no exception to this historical underrepresentation trend. Only 1.6 per cent of its cohort is people from Black and African ancestry, meanwhile individuals from European ancestry make up 94 per cent of it. A striking discrepancy for the UK where the latter group makes up 74.4 per cent of the total population (according to the 2021 UK census). In UK studies, “there is more genetic diversity among the Black African ethnic group, the majority of genetic information is derived from small studies, mostly from West Africa.”
Globally, African DNA only makes up two per cent of genomic datasets.
This lack of diversity is not only harmful to effective diagnosis, drug development and precision medicine, it further exacerbates health inequalities in a world of overlapping crises. Meanwhile increased inclusion can help to get the right medicine to the right patient at the right time. For example, a study including Nigerian participants looking at genetic risk factors associated with neurological disorder, found a novel genetic variation that may be associated with Alzheimer’s disease in African ancestry populations. There is similar evidence in genetic variation research in Parkinson’s disease, various types of cancer like prostate cancer and cystic fibrosis.
A pressing issue with historical roots
African ancestry populations are mostly suspicious of genomic research and tend not to share their data to help facilitate. That mistrust dates back to history with the infamous Tuskegee Syphilis Study and case of Henrietta Lacks having a huge role to play, and the fact that researchers have too often engaged in “helicopter research” without involving communities in the process.
In addition to mistrust, the lack of a standard applied way of categorising genomic data by ethnicity and race; lack of funding to expand cohorts; and underrepresentation of African ancestry researchers can be added to the mix of reasons.
Towards inclusive genomic research that works for everyone
The picture is not all bleak – there is a glimpse of hope!
From global psychiatric genetics initiatives like the Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project through to innovative biobank initiatives such as 54Gene and innovative genome variation projects such as the African Genome Variation Project, there are encouraging signals.
In December 2022, the UK government announced a £175 million investment in genomics research, under then Minister of Health Will Quince, some of which is planned to support a genomic sequencing programme of up to 25,000 research participants of non-European ancestry and run programmes to “build trusting relationships with traditionally excluded groups of people, such as patients with sickle cell disease who are unrepresented in research studies.”
In other parts of the world, collaborative efforts have also been stirring the movement in the right direction such as the Million Veteran Program and the All of Us program in the US, the Human Heredity and Health in Africa (H3Africa) consortium, in South Africa, the Three Million African Genomes project 3MAG in Nigeria, and the NeuroDev study in South Africa and Kenya. In Canada, the UK-Canadian three-year initiative to help “create equitable multi-ethnic polygenic risk scores that improve clinical care” as part of a wider Economic and Social Research Council (ESRC) led Canada-UK AI Initiative, is another example of encouraging signs.
As Pui-Yan Kwok, a specialist in genome analysis based at University of California, San Francisco said, “one person is not representative of the world”, therefore genomic datasets need to include diversity if we want a shot at a just and equitable health system.
Increased funding and more international collaboration would probably help boost ongoing representation efforts.
* There are around 200 million people identifying themselves as being of African descent who live in the Americas. Many millions more live in other parts of the world, outside of the African continent.