Genetic Diversity in African Populations Can Advance Precision Medicine Globally

Africa, the second-largest continent and home to 1.4 billion people, faces a unique and daunting challenge when advancing precision medicine practices on the continent. While it carries 25% of the global disease burden, it contributes only 2.5% to the global gross domestic product. According to Collen Masimirembwa, PhD, founder, president, and chief scientific officer at the Africa Institute of Biomedical Science and Technology, technological advancements can bridge this gap by leveraging Africa's unparalleled genetic diversity.

“I think the big opportunity, at least from a precision medicine point of view, is the fact that African populations exhibit genetic variability, which is more than 200 times what we observe in other world populations,” said Masimirembwa during a keynote presentation at Precision Medicine World Conference 2025. “We are thinking that represents an opportunity for understanding human biology, and, in particular, disease risk and response to medicines.”

Artificial intelligence depiction of a double helix. Image Credit: © CarlosEduardo - stock.adobe.com

However, for African populations, this variability is a double-edged sword, as it presents challenges in drug use standardization. For Masimirembwa, he began his exploration of this issue in the early 1990s at Sweden's Karolinska Institute, where he studied the enzyme CYP2D6, which is pivotal in drug metabolism. Over a period of 30 years, his research evolved from foundational science to real-world applications, such as optimizing the use of tamoxifen (Nolvadex; AstraZeneca) for breast cancer treatment in African populations.

This research progression also illustrates the transformative power of Global North and Global South collaborations in medicine, according to Masimirembwa. His work in Sweden provided him with research methodologies and a knowledge of translational science that he then brought back to Africa. Through this journey, he maintained the goal of bridging the gap between research and clinical applications, ensuring tangible benefits for patients in Africa.

“I'm a strong believer in Global North and Global South partnerships that can transform how we do our research,” Masimirembwa said. “From our research, we found that African populations from Nigeria, Kenya, Tanzania, and South Africa, when you look at their whole genome profile, tend to cluster by themselves compared to Asian and European populations.”

According to Masimirembwa, by pulling from the 1000 Genomes Project, his team observed that within those African populations, there was significant genetic variability, and that genome variation is much higher in African populations than in European and Asian populations.

“If you're trying to understand gene function, you probably are better off working on gene function in the African population, because you will have more variation, which can give you scope of function,” Masimirembwa said.

A critical example of this variability is found in the CYP2D6 gene, responsible for metabolizing over 20% of commonly used drugs. Unique genetic variants such as *29 and *17, which are only prevalent in African populations and people of African ancestry, affect 30% to 40% of these individuals. These variants influence drug metabolism, rendering standard dosages ineffective. For example, tamoxifen, which is widely used for breast cancer treatment at 20 mg per day, is less effective in African patients with these variants. Increasing the dosage to 40 mg per day has been proposed to enhance therapeutic outcomes.

“If you increase the dose [of tamoxifen] to 40 milligrams, you will be able to feed the enzyme with more substrate for it to produce more active metabolite, the endoxifen,” Masimirembwa said. “This is a good example of where in the clinic there might be a need for bridging studies as the drug moves from one population to another, and for Africa, this seems to be quite clear.”

Masimirembwa and his team then extended their analysis to the World Health Organization's essential drugs list, identifying 57 medications requiring genetic testing for optimal use. These drugs, used to treat top diseases across Africa, expose millions of patients to suboptimal outcomes due to a lack of preemptive genetic testing. Ultimately, millions of patients may require drug or dosage modifications based on their genetic profiles, highlighting the urgent need for pharmacogenetics-guided precision medicine on the continent.

Pharmaceutical costs. Image Credit: ©KKC Studio - stock.adobe.com

Economic considerations further underscore the significance of this approach. Masimirembwa's research revealed that African countries spend approximately $2.5 billion annually on drugs requiring pharmacogenetic insights. Procurement patterns vary, with North African nations such as Egypt focusing on non-communicable diseases, while South Africa balances its approach between communicable and non-communicable diseases. Addressing pharmacogenetic variability could enhance drug efficacy, reduce adverse drug reactions (ADRs), and cut costs, which would benefit health care systems and patients.

The issue of ADRs also comes into play, according to Masimirembwa. Africa accounts for only 1% of global ADR reports, reflecting the need for stronger pharmacovigilance systems. Yet, even with these limited data, Masimirembwa and his team observed that ADRs in Africa are often linked to CYP2D6 and CYP2C19, further validating the role of pharmacogenetics in improving drug safety. Targeting these key genes could streamline resource allocation and prioritize interventions in resource-limited settings.

Looking forward, Masimirembwa outlined a roadmap for advancing precision medicine in Africa. Key to this vision are strategic partnerships with biotech and pharmaceutical industries, the establishment of Africa-specific precision medicine clinical guidelines, and advocacy for policy changes. Collaborative efforts could address challenges such as the lack of functional data for genetic variants and the need for robust genotype-phenotype databases. Artificial intelligence could also play a role in analyzing complex genetic data, accelerating the development of predictive algorithms, and refining treatment protocols, according to Masimirembwa.

To achieve these goals, Masimirembwa's team is pursuing 2 main initiatives. First, they aim to generate actionable pharmacogenetic data by sequencing patient populations on specific drugs and measuring drug and metabolite concentrations. This approach has already begun with 1000 patients and aims to expand to 6000 patients in the next few years. Second, they are focusing on clinical trials, leveraging their established phase 1 clinical trial unit in partnership with pharmaceutical companies such as AstraZeneca and Novartis. These trials aim to address questions relevant to African populations, ensuring that precision medicine strategies are both effective and context specific.

“The breadth and depth of Africa's genomic diversity is not only an opportunity for Africa to advance precision medicine, but for a global effort,” Masimirembwa said. “The variability [on the continent] can be used to understand biology and physiology across the world. I think if we approach the idea in that way, we will have a better scope for partnerships and collaborations.”

REFERENCE

Masimirembwa C. Keynote: Genomic Diversity in Africa-Pharmacogenetics and Clinical Applications. Presented at: Precision Medicine World Conference; February 5-7, 2025; Santa Clara, California.