Publications

" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research."
Prof Halidou TINTO, PharmD, Msc, PhD Head of the CRUN

2024
Journal Articles
	David Twesigomwe, Britt I. Drögemöller, Galen E. B. Wright, Clement Adebamowo, Godfred Agongo, Palwendé R. Boua, Mogomotsi Matshaba, Maria Paximadis, Michèle Ramsay, Gustave Simo, Martin C. Simuunza, Caroline T. Tiemessen, Zané Lombard, Scott Hazelhurst Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations Journal Article In: Clinical pharmacology and therapeutics, vol. 115, iss. 3, pp. 576-594, 2024, ISSN: 1532-6535. Abstract \| BibTeX \| Tags: Africa South of the Sahara, Alleles, Britt I Drögemöller, Cytochrome P-450 CYP2A6 / genetics, Cytochrome P-450 CYP2B6 / genetics, David Twesigomwe, doi:10.1002/cpt.3124, Gene Frequency, Genotype, Humans, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Nicotine, NIH, NLM, Non-U.S. Gov't, Pharmacogenetics, pmid:38049200, PubMed Abstract, Research Support, Scott Hazelhurst \| Links: Close Close @article{Twesigomwe2024, title = {Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations}, author = {David Twesigomwe and Britt I. Dr\"{o}gem\"{o}ller and Galen E. B. Wright and Clement Adebamowo and Godfred Agongo and Palwend\'{e} R. Boua and Mogomotsi Matshaba and Maria Paximadis and Mich\`{e}le Ramsay and Gustave Simo and Martin C. Simuunza and Caroline T. Tiemessen and Zan\'{e} Lombard and Scott Hazelhurst}, url = {https://pubmed.ncbi.nlm.nih.gov/38049200/}, doi = {10.1002/CPT.3124}, issn = {1532-6535}, year = {2024}, date = {2024-01-01}, journal = {Clinical pharmacology and therapeutics}, volume = {115}, issue = {3}, pages = {576-594}, publisher = {Clin Pharmacol Ther}, abstract = {Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., 6 and 18; frequency of 21\textendash47% and 2\textendash19%, respectively) and CYP2A6 (e.g., 4, 9, and 17; frequency of 0\textendash6%, 3\textendash10%, and 6\textendash20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (54, 55, and 56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent.}, keywords = {Africa South of the Sahara, Alleles, Britt I Dr\"{o}gem\"{o}ller, Cytochrome P-450 CYP2A6 / genetics, Cytochrome P-450 CYP2B6 / genetics, David Twesigomwe, doi:10.1002/cpt.3124, Gene Frequency, Genotype, Humans, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Nicotine, NIH, NLM, Non-U.S. Gov't, Pharmacogenetics, pmid:38049200, PubMed Abstract, Research Support, Scott Hazelhurst}, pubstate = {published}, tppubtype = {article} } Close Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., 6 and 18; frequency of 21–47% and 2–19%, respectively) and CYP2A6 (e.g., 4, 9, and 17; frequency of 0–6%, 3–10%, and 6–20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (54, 55, and 56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent. Close
	Dylan G Maghini, Ovokeraye H Oduaran, Jakob Wirbel, Luicer A Ingasia Olubayo, Natalie Smyth, Theophilous Mathema, Carl W Belger, Godfred Agongo, Palwendé R Boua, Solomon SR Choma, F Xavier Gómez-Olivé, Isaac Kisiangani, Given R Mashaba, Lisa Micklesfield, Shukri F Mohamed, Engelbert A Nonterah, Shane Norris, Hermann Sorgho, Stephen Tollman, Floidy Wafawanaka, Furahini Tluway, Michèle Ramsay, Ami S Bhatt, Scott Hazelhurst Expanding the human gut microbiome atlas of Africa Journal Article In: bioRxiv : the preprint server for biology, 2024, ISSN: 2692-8205. Abstract \| BibTeX \| Tags: doi:10.1101/2024.03.13.584859, Dylan G Maghini, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Ovokeraye H Oduaran, PMC10980044, pmid:38559015, Preprint, PubMed Abstract, Scott Hazelhurst \| Links: Close Close @article{Maghini2024, title = {Expanding the human gut microbiome atlas of Africa}, author = {Dylan G Maghini and Ovokeraye H Oduaran and Jakob Wirbel and Luicer A Ingasia Olubayo and Natalie Smyth and Theophilous Mathema and Carl W Belger and Godfred Agongo and Palwend\'{e} R Boua and Solomon SR Choma and F Xavier G\'{o}mez-Oliv\'{e} and Isaac Kisiangani and Given R Mashaba and Lisa Micklesfield and Shukri F Mohamed and Engelbert A Nonterah and Shane Norris and Hermann Sorgho and Stephen Tollman and Floidy Wafawanaka and Furahini Tluway and Mich\`{e}le Ramsay and Ami S Bhatt and Scott Hazelhurst}, url = {https://pubmed.ncbi.nlm.nih.gov/38559015/}, doi = {10.1101/2024.03.13.584859}, issn = {2692-8205}, year = {2024}, date = {2024-01-01}, journal = {bioRxiv : the preprint server for biology}, publisher = {bioRxiv}, abstract = {Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.}, keywords = {doi:10.1101/2024.03.13.584859, Dylan G Maghini, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Ovokeraye H Oduaran, PMC10980044, pmid:38559015, Preprint, PubMed Abstract, Scott Hazelhurst}, pubstate = {published}, tppubtype = {article} } Close Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research. Close
	Scott Hazelhurst, Palwendé Boua, Ananyo Choudhury, Siyanda Madala, Dhriti Sengupta, Furahini Tluway, Michèle Ramsay Computation of Socio-Economic Status in the AWI-Gen Project Journal Article In: medRxiv : the preprint server for health sciences, 2024. Abstract \| BibTeX \| Tags: doi:10.1101/2024.08.22.24312411, MEDLINE, Michèle Ramsay, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Palwendé Boua, PMC11370514, pmid:39228720, Preprint, PubMed Abstract, Scott Hazelhurst \| Links: Close Close @article{Hazelhurst2024, title = {Computation of Socio-Economic Status in the AWI-Gen Project}, author = {Scott Hazelhurst and Palwend\'{e} Boua and Ananyo Choudhury and Siyanda Madala and Dhriti Sengupta and Furahini Tluway and Mich\`{e}le Ramsay}, url = {https://pubmed.ncbi.nlm.nih.gov/39228720/ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11370514}, doi = {10.1101/2024.08.22.24312411}, year = {2024}, date = {2024-01-01}, journal = {medRxiv : the preprint server for health sciences}, publisher = {medRxiv}, abstract = {Socio-economic status of participants in many public health, epidemiological, and genome-wide association studies is an important trait of interest. It is often used in these studies as a measure of direct interest or as a covariate. The Africa Wits INDEPTH Partnership for Genomic and Environmental Research (AWI-Gen) explores genomic and environmental factors in non-communicable diseases, particularly cardio-metabolic disease. In Phase I of AWI-Gen, approximately 12,000 participants were recruited at six sites in four African countries. Participants were asked questions about asset ownership. This technical note describes how AWI-Gen computed socio-economic status from the asset register.}, keywords = {doi:10.1101/2024.08.22.24312411, MEDLINE, Mich\`{e}le Ramsay, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Palwend\'{e} Boua, PMC11370514, pmid:39228720, Preprint, PubMed Abstract, Scott Hazelhurst}, pubstate = {published}, tppubtype = {article} } Close Socio-economic status of participants in many public health, epidemiological, and genome-wide association studies is an important trait of interest. It is often used in these studies as a measure of direct interest or as a covariate. The Africa Wits INDEPTH Partnership for Genomic and Environmental Research (AWI-Gen) explores genomic and environmental factors in non-communicable diseases, particularly cardio-metabolic disease. In Phase I of AWI-Gen, approximately 12,000 participants were recruited at six sites in four African countries. Participants were asked questions about asset ownership. This technical note describes how AWI-Gen computed socio-economic status from the asset register. Close