Genetic studies of African populations on disease susceptibility and response to vaccines and therapeutics 

Last Updated on October 8, 2022 by Joseph Gut – thasso

September 25, 2022 – Nearly 2000 years ago the Roman scholar and natural philosopher Pliny the Elder wrote in his Natural History: “Ex Africa surgit semper aliquid novi” (from Africa there is always something new). This quote beautifully applies to genetic studies of African populations as they provide a critical resource in the study of genetic risk factors of human disease and to new discoveries. Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent.

For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in Sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease. In an extensive review , a team of authors and researchers have addressed this issue. They show in quit some detail, how selected genes may influence or even be responsible for the susceptibility to disease phenotypes characteristic in a variety of Sub-Saharan Afrian populations.

Some problems in selecting definitive ethnicity and examples of definitive correlations with disease susceptibility

Here, we try to show excerpts from the afore cited review in order to illustrate infectious diseases, rare diseases, but also normal chronic diseases, where definitively genetic backgrounds play a role in their remedy, or in the tendency of falling prey to them. We may, however, not find clear-cut ethnic dependency.  This has certainly to do with two things.

First, Africa is a region of considerable genetic, linguistic, and cultural diversity. There are over 2,000 distinct ethnolinguistic groups, speaking languages that constitute nearly a third of the world’s living languages. These languages have been classifed into four major language families: Niger-Kordofanian (spoken predominantly by agriculturalist populations across a broad geographic distribution in Africa), Afro-Asiatic (spoken predominantly by northern and eastern Africa pastoralists and agropastoralists), Nilo-Saharan (spoken predominantly by eastern and central African pastoralists), and Khoisan (a language containing click-consonants, spoken by southern and eastern African hunter–gatherer populations). These populations live in a diverse set of environments and climates, including tropical forests, savannah, desert, and coastal regions. Moreover, African populations have a complex demographic history, consisting of ancient and recent population expansion and contraction events, short and long range migrations (e.g. the migration of agricultural Bantu-speakers from West Africa throughout sub-Saharan Africa within the past 4,000 year and the migration of Khoisan-speakers from eastern to southern Africa within the past 20’000 to 40’000 years), and countless local population admixtures The modern day (i., today) consequences of these migrations may be illustrated with the example of Cameroon; where among environ 30 millions inhabitants exist 250 ethnic groups and about 250 different languages.

Second: Since today there exist not yet definitive genetic signature profiles for a given “ethnicity”, it will still be very difficult to assign, based on genetic profiles, risk profiles for the susceptibility of members of given ethnicities for certain selected disease phenotypes and to assign higher or lower disease risks to selected ethnicities. For the time being, one may have to stay with information on genetic variation that is connected with increased risks of individuals carrying these variations for disease phenotypes, vaccination successes, and drug/therapy success; perhaps not yet strictly connected with ethnicities but rather with groups of individuals of the same local social-economic, environmental, cultural, linguistic, and/or behavioural environments.

In line with this latter estimation, there exist already many studies schooling disease risks or absence thereof in patients of selected genotypes. Malaria would be an example. Malaria is a serious health issue in Africa, accounting for one in every five childhood deaths. In 2006 the WHO estimated that almost 74% of the African population lives in areas endemic for malaria, about 19% in epidemic-prone and only 7% in malaria-free areas. Studies of large populations are addressing the complex genetics of malaria susceptibility and several genes have been associated with malaria susceptibility. Certain phenomena (pathways) are critical to the development overt malaria, and genetic variants that disrupt these processes can protect against disease. The invasion of erythrocytes by malaria parasites is central to the disease process, and the Duffy blood group antigen, a chemokine receptor expressed in many cell types and encoded by the FY gene, is important because Plasmodium vivax cannot infect individuals who do not express the Duffy antigen, resulting in full protection of Duffy (-) individuals. The lack of Duffy expression is due to a promoter SNP that alters a binding site for the GATA-1 transcription factor, resulting in the parasite being unable to invade red blood cells. Over 97% of individuals in West and Central Africa are Duffy (-). The date of emergence of the Duffy (-) genotype has been broadly dated, from more than 90,000 to about 6,500 years ago, (Webb 2005). There has been considerable debate whether the spread of Duffy (-) was due to survival selection of individuals (in the sense of Charles Darvin) in response to Plasmodium vivax or if it evolved independently and probably earlier. The latter hypothesis is consistent with a Southeast Asian origin of P. vivax, and the independent evolution of the Duffy (-) genotype throughout Africa. Whether there developed a strict correlation of ethnicity with the malaria phenotype, particularly when considering individuals living in the aforementioned  epidemic-prone and malaria-free areas remains an open question.

Here, we may be aware that the above considerations around malaria also apply for other infectious diseases throughout Africa such as tuberculosis, HIV/AIDS, leprosy, schistosomiasis, trachoma, and even to non-communicable diseases such as diabetes and obesity, hypertension, cardiovascular disease, cancer in general, but then to prostate cancer, colorectal cancer, breast cancer, vaccine-induced immunity, serum lipids (cholesterol). Only the candidate genetic risk variants in each case would vastly be different.

By doing studies throughout Africa it will be possible to capture most of the extant genetic risk factors in all human populations. It may also be possible to use simple and relatively inexpensive genetic tests to reduce overall healthcare costs. There are many diseases that are endemic to Africa that carry signifcant genetic risk, and studying these could improve the health in Africa. However, despite the advantages and importance of these studies there are substantial impediments to performing genetic research in an African setting, most notably lack of resources and infrastructure. In recognition of these factors great efforts and initiatives are in place to develop research networks  and biobanks needed to expedite clinical and genetic research related to the specifics of Africa. Such initiatives include, but are not restricted to, the African Society of Human Genetics, the African Genomic Medicine Portal (AGMP), the H3Africa Consortium (H3Africa), or African-based companies like 53gene (53gene).

Needless to say that thasso has already had several articles on genetics and genetic backgrounds when it comes to African patients, such as, but not limited to, “Hidden secrets in African genomes revealed by large scale sequencing“,  or “AGMP: The African Genomic Medicine Portal“, “Populations of African descent: New trait loci for hypertension“, and “Tapping into the massive potential of African genomes: 54gene“.

See here a sequence on the genetic diversity of African populations:

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