Publications

@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}

}

@article{nokey,

title = {Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits.},

author = {Ananyo Choudhury and Jean-Tristan Brandenburg and Tinashe Chikowore and Dhriti Sengupta and Palwende Romuald Boua and Nigel J. Crowther and Godfred Agongo and Gershim Asiki and F. Xavier G\'{o}mez-Oliv\'{e} and Isaac Kisiangani and Eric Maimela and Matshane Masemola-Maphutha and Lisa K. Micklesfield and Engelbert A. Nonterah and Shane A. Norris and Hermann Sorgho and Halidou Tinto and Stephen Tollman and Sarah E. Graham and Cristen J. Willer and Scott Hazelhurst and Mich\`{e}le Ramsay},

doi = {10.1038/s41467-022-30098-w},

year  = {2022},

date = {2022-05-01},

urldate = {2022-05-01},

journal = {Nature communications},

volume = {13},

issue = {1},

pages = {2578},

abstract = {Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10(-8)). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10(-8)). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data.},

keywords = {*Genome-Wide Association Study, Africa South of the Sahara, Cholesterol, Cross-Sectional Studies, Humans, LDL/genetics},

pubstate = {published},

tppubtype = {article}

}

@article{Skrip2020-fq,

title = {Clinical management and mortality among COVID-19 cases in  sub-Saharan Africa: A retrospective study from Burkina Faso and  simulated case analysis},

author = {Laura Skrip and Karim Derra and Mikaila Kabor\'{e} and Navideh Noori and Adama Gansan\'{e} and Innocent Val\'{e}a and Halidou Tinto and Bicaba W Brice and Mollie Van Gordon and Brittany Hagedorn and Herv\'{e} Hien and Benjamin M Althouse and Edward A Wenger and Andr\'{e} Lin Ou\'{e}draogo},

doi = {10.1016/j.ijid.2020.09.1432},

issn = {1878-3511 1201-9712},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Int. J. Infect. Dis.},

volume = {101},

pages = {194--200},

publisher = {Elsevier BV},

abstract = {BACKGROUND: Absolute numbers of COVID-19 cases and deaths 

 reported to date in the sub-Saharan Africa (SSA) region have 

 been significantly lower than those across the Americas, Asia 

 and Europe. As a result, there has been limited information 

 about the demographic and clinical characteristics of deceased 

 cases in the region, as well as the impacts of different case 

 management strategies. METHODS: Data from deceased cases 

 reported across SSA through 10 May 2020 and from hospitalized 

 cases in Burkina Faso through 15 April 2020 were analyzed. 

 Demographic, epidemiological and clinical information on 

 deceased cases in SSA was derived through a line-list of 

 publicly available information and, for cases in Burkina Faso, 

 from aggregate records at the Centre Hospitalier Universitaire 

 de Tengandogo in Ouagadougou. A synthetic case population was 

 probabilistically derived using distributions of age, sex and 

 underlying conditions from populations of West African countries 

 to assess individual risk factors and treatment effect sizes. 

 Logistic regression analysis was conducted to evaluate the 

 adjusted odds of survival for patients receiving oxygen therapy 

 or convalescent plasma, based on therapeutic effectiveness 

 observed for other respiratory illnesses. RESULTS: Across SSA, 

 deceased cases for which demographic data were available were 

 predominantly male (63/103, 61.2%) and aged \>50 years (59/75, 

 78.7%). In Burkina Faso, specifically, the majority of deceased 

 cases either did not seek care at all or were hospitalized for a 

 single day (59.4%, 19/32). Hypertension and diabetes were often 

 reported as underlying conditions. After adjustment for sex, age 

 and underlying conditions in the synthetic case population, the 

 odds of mortality for cases not receiving oxygen therapy were 

 significantly higher than for those receiving oxygen, such as 

 due to disruptions to standard care (OR 2.07; 95% CI 

 1.56-2.75). Cases receiving convalescent plasma had 50% reduced 

 odds of mortality than those who did not (95% CI 0.24-0.93). 

 CONCLUSIONS: Investment in sustainable production and 

 maintenance of supplies for oxygen therapy, along with messaging 

 around early and appropriate use for healthcare providers, 

 caregivers and patients could reduce COVID-19 deaths in SSA. 

 Further investigation into convalescent plasma is warranted 

 until data on its effectiveness specifically in treating 

 COVID-19 becomes available. The success of supportive or 

 curative clinical interventions will depend on earlier treatment 

 seeking, such that community engagement and risk communication 

 will be critical components of the response.},

note = {Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMID: 32987177 

PMCID: PMC7518969},

keywords = {Adolescent, Adult, Africa South of the Sahara, Aged, Antiviral Agents/administration \& dosage, Asia/epidemiology, Burkina Faso, Burkina Faso/epidemiology, Child, Clinical management of SARS-CoV-2 infection: convalescent plasma, COVID-19/drug therapy/epidemiology/mortality/therapy, Europe/epidemiology, Female, Health systems strengthening, Humans, Immunization, Infant, Male, Mortality, Oxygen therapy, Pandemics, Passive, Preschool, Retrospective Studies, SARS-CoV-2 infection, SARS-CoV-2/drug effects/physiology, sub-Saharan Africa, Young Adult},

pubstate = {published},

tppubtype = {article}

}