Approved Research

An integrative data-driven approach to the genomics of anti-tuberculosis and anti-malarial drug responses in African populations

Lay summary

Response to drugs is tightly controlled by a set of genes responsible for the absorption, distribution, metabolisation, and excretion of drugs in the organism (ADME genes). The genetic variability of ADME genes differs significantly among world populations. In particular, Africa, as a place of birth of the genus Homo, and given its variety of climates and evolutionary constraints, is the most diverse continent in the world. Therefore,  population groups in Africa might respond differently to drugs, particularly those used to treat infections with malaria and tuberculosis. These two transmissible diseases are major health and economic burdens in Africa. Therefore, profiling genetic variability in Africa is a key step in understanding biological mechanisms that control response to anti-malaria and anti-tuberculosis drugs. High throughput Genomic technologies such as third-generation sequencing and microarray genotyping offer the opportunity to characterize the ensemble of ADME gene variability in batch.  Uk Biobank contains a large repertoire of such data related to individuals from Africa or with African ancestry that can help in profiling the generic variability of genes involved in anti-malaria and anti-tuberculosis drug treatment. These data could be processed using computational methods to determine the variants with potentially significant impact on the function of ADME genes. With the help of UK Biobank data, we will study the impact of African genetic variability on drug processing mechanisms involving 35 drugs that are in use or with high pharmacological potential for the treatment of tuberculosis and malaria infections.  The study is scheduled for two years period and will involve other datasets collected from different collaborators in addition to data from the UK Biobank. Our study will help in the efforts of establishing tailored therapies against malaria and tuberculosis to increase the efficacy of drugs in African population groups.