Paleontological and genetic evidence indicates that modern humans originated in Africa within the past 300,000 years and spread across the globe over the last 100,000 years. Consequently, modern humans have continuously inhabited the African continent longer than any other region in the world.
The complex interplay of biological, historical migratory patterns, cultural practices, and environmental factors – such as living in deserts or rainforests – has exerted differential selection pressures on African genomes. As a result, the African continent exhibits greater genetic variation than any other region globally.
The average African genome contains nearly one million more genetic variants than the average non-African genome and carries almost 10% more DNA than the current reference genome.
Africa is also exceptionally culturally and ethno-linguistically diverse. While other regions of the world average between 3.2 to 4.7 ethnic groups per country, African countries average over 8 ethnic groups each, collectively accounting for 43% of the world’s ethnic groups. In 2020, genome-wide studies of just 426 African individuals from 50 ethnolinguistic groups uncovered more than three million previously unidentified genetic variants.
This diversity is so extensive that genetic differences within African populations are greater than those between Africans and Eurasians. This evidence supports the “Out of Africa” model of human evolution, suggesting that the genetic diversity observed in Eurasians is largely a subset of that found in Africans.
Genetic Diversity and Precision Medicine
This extraordinary diversity must be considered when implementing the principles of P4 medicine (participatory, precision, predictive, and preventive medicine) which have developed alongside advances in clinical genetics, artificial intelligence, and digital health technologies.
Precision medicine (also known as personalised medicine) aims to tailor diagnostics, prognostics, and therapeutics to individual patients based on their genetic makeup. Accounting for the susceptibility of diverse populations to specific diseases or their responses to particular medications is crucial for effective and equitable healthcare.
Positive Implications of African Genetic Diversity for Precision Medicine
Pharmacogenomics aims to optimise patient outcomes by creating personalised treatment plans informed by genetic variation. The high genetic variability in African populations enables researchers and clinicians to identify specific variants that can maximise therapeutic efficacy, minimise side effects, and personalise medication regimens.
African genetic diversity also plays an important role in discovering novel variants that may be rare or absent in other populations. For example, studies have shown that individuals with the sickle cell trait (most prevalent in sub-Saharan Africa) are largely protected against severe malaria. Similarly, G6PD deficiency common in African populations, confers some protections against malaria. These insights are helpful in developing novel therapies for diseases that disproportionately affect African communities.
Genetic biomarkers are essential for guiding clinical decision-making in disease diagnosis, prognosis, monitoring, and predicting therapeutic responses. To ensure these biomarkers are effective and reliable, they must be validated across diverse populations. Research by Majara et al. examined polygenic risk scores (PRS) across African populations, using both simulations and empirical data from South Africa, Uganda, and the UK. Their findings highlighted the limited generalisability of PRS in African populations due to extensive genetic and environmental diversity. Therefore, Africa’s genetic diversity offers a unique opportunity to test and validate biomarkers across multiple genetic backgrounds, boosting their applicability in precision medicine.
Challenges to Precision Medicine in African Populations
African populations remain underrepresented in genomic research databases. In 2019, Africans accounted for only 3% of genome-wide association study (GWAS) data, dropping to just 1.1% in 2021. Factors contributing to this include political barriers, insufficient funding, and limited infrastructure to support genomic research. This underrepresentation limits the applicability of findings to African populations and may prevent discoveries that could benefit African patients.
Genetic variations in key genes affecting drug metabolism further complicate treatment strategies. For example:
- HLA-B*57:01 allele, more common in individuals of African ancestry, increases the risk of hypersensitivity to abacavir.
- Variants in CYP2C19 affect clopidogrel efficacy, increasing cardiovascular risks.
- Differences in CYP2B6 and ABCB1 genes influence antiretroviral therapy outcomes.
- Variations in opioid metabolism genes, such as CYP2D6 and OPRM1, impact pain management and adverse effects.
These examples highlight both the challenges and the urgent need for precision medicine in Africa.
Conclusion
Africa’s unparalleled genetic diversity presents both significant opportunities and challenges for precision medicine. While it offers unique insights into disease susceptibility, pharmacogenomics, and biomarker development, underrepresentation in global genomic studies limits the equitable implementation of personalised care.
Improving the representation of African genomes in research can enhance the human reference genome (HRG), reduce bias in genetic analyses, and enable the development of more accurate reference panels. By integrating African genetic diversity into global datasets, precision medicine can be advanced for all populations, ensuring that therapeutic interventions are effective and inclusive.
Veronique Ropion
Director of Business Strategy, Marketing, and Corporate Communication
Source
- Majara L, Kalungi A, Koen N, et al. Low generalizability of polygenic scores in African populations due to genetic and environmental diversity. bioRxiv. 2021;14. doi:10.1101/2021.01.12.426453
- Sibomana O. Genetic Diversity Landscape in African Population: A Review of Implications for Personalized and Precision Medicine. Pharmacogenomics and Personalized Medicine 2024:17 487–496.