Molecular epidemiology of invasive group B Streptococcus in South Africa, 2019-2020.

Background: Group B Streptococcus (GBS) is a leading cause of neonatal meningitis and sepsis and an important cause of disease in adults. Capsular polysaccharide and protein-based GBS vaccines are currently under development.

Methods: Through national laboratory-based surveillance, invasive GBS isolates were collected from patients of all ages between 2019 and 2020.

Computation of Socio-Economic Status in the AWI-Gen Project.

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.

An assessment of the genomic structural variation landscape in Sub-Saharan African populations.

Structural variants are responsible for a large part of genomic variation between individuals and play a role in both common and rare diseases. Databases cataloguing structural variants notably do not represent the full spectrum of global diversity, particularly missing information from most African populations. To address this representation gap, we analysed 1,091 high-coverage African genomes, 545 of which are public data sets, and 546 which have been analysed for structural variants for the first time.

Expanding the human gut microbiome atlas of Africa.

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.

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.

Multimorbidity in African ancestry populations: a scoping review.

Objectives: Multimorbidity (MM) is a growing concern linked to poor outcomes and higher healthcare costs. While most MM research targets European ancestry populations, the prevalence and patterns in African ancestry groups remain underexplored. This study aimed to identify and summarise the available literature on MM in populations with African ancestry, on the continent, and in the diaspora.

Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

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.

Characterization of pharmacogenetic variation in African populations and comparison with other global populations.

is important in the metabolism of clopidogrel and several antidepressants. This study aimed to characterize the distribution of star alleles (haplotypes) across diverse African populations compared with global populations. star alleles and diplotypes were called from high coverage genomes using the StellarPGx pipeline.

Performance and accuracy evaluation of reference panels for genotype imputation in sub-Saharan African populations.

Based on evaluations of imputation performed on a genotype dataset consisting of about 11,000 sub-Saharan African (SSA) participants, we show Trans-Omics for Precision Medicine (TOPMed) and the African Genome Resource (AGR) to be currently the best panels for imputing SSA datasets. We report notable differences in the number of single-nucleotide polymorphisms (SNPs) that are imputed by different panels in datasets from East, West, and South Africa. Comparisons with a subset of 95 SSA high-coverage whole-genome sequences (WGSs) show that despite being about 20-fold smaller, the AGR imputed dataset has higher concordance with the WGSs.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

H3AGWAS: a portable workflow for genome wide association studies.

Background: Genome-wide association studies (GWAS) are a powerful method to detect associations between variants and phenotypes. A GWAS requires several complex computations with large data sets, and many steps may need to be repeated with varying parameters. Manual running of these analyses can be tedious, error-prone and hard to reproduce.

Characterization of Novel Alleles across Sub-Saharan African Populations.

The gene has been widely studied to characterize variants and/or star alleles, which account for a significant portion of variability in drug responses observed within and between populations. However, African populations remain under-represented in these studies. The increasing availability of high coverage genomes from African populations has provided the opportunity to fill this knowledge gap.

Characterization of CYP2D6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes-derived from activity scores-were examined across multiple sub-Saharan African populations based on bioinformatics analysis of 961 high-depth whole genome sequences.

Characterization of haplotype distribution in African populations and comparison with other global populations.

POR is an enzyme that mediates electron transfer to enable the drug-metabolizing activity of CYP450 proteins. However, has been understudied in pharmacogenomics despite this vital role. This study aimed to characterize the genetic variation in across African populations and to compare the star allele (haplotype) distribution with that in other global populations.

Electronic Data Capture System (REDCap) for Health Care Research and Training in a Resource-Constrained Environment: Technology Adoption Case Study.

Background: Electronic data capture (EDC) in academic health care organizations provides an opportunity for the management, aggregation, and secondary use of research and clinical data. It is especially important in resource-constrained environments such as the South African public health care sector, where paper records are still the main form of clinical record keeping.

Objective: The aim of this study was to describe the strategies followed by the University of the Witwatersrand Faculty of Health Sciences (Wits FHS) during the period from 2013 to 2021 to overcome resistance to, and encourage the adoption of, the REDCap (Research Electronic Data Capture; Vanderbilt University) system by academic and clinical staff.

Molecular dynamics of G6PD variants from sub-Saharan Africa.

Precision medicine uses genomic guidance to improve drug treatment safety and efficacy. Prior knowledge of genetic variant impact can enable such strategies, but current knowledge of African variants remains scarce. variants are linked to haemolytic adverse effects for a number of drugs commonly used in African populations.