sub-Saharan African Populations Research Articles

Mapping the evidence on factors related to postpartum contraception among sub-Saharan African immigrant and refugee women in the United States of America: A scoping review protocol.

Postpartum contraception is essential to sexual and reproductive health (SRH) care because it encourages healthy spacing between births, helps women avoid unwanted pregnancies, and lessens the risks of health problems for mothers and babies. Sub-Saharan African immigrant and refugee populations are rapidly increasing in the United States, and they come from a wide range of cultural, linguistic, religious, and social origins, which may pose challenges in timely access to culturally acceptable SRH care, for preventing mistimed or unwanted childbearing. The objective of this scoping review is to assess the extent of the available literature on postpartum contraception among sub-Saharan African immigrant and refugee women living in the United States. We developed preliminary search terms with the help of an expert librarian, consisting of keywords including birth intervals, birth spacing, contraception, postpartum contraception or family planning, and USA or America, and sub-Saharan African immigrants, or emigrants. The study will include the following electronic databases: PubMed/MEDLINE, PsycINFO, CINAHL, EMBASE, and the Global Health Database. The sources will include studies on postpartum care and contraceptive access and utilization among sub-Saharan African immigrants living in the US. Citations, abstracts, and full texts will be independently screened by two reviewers. We will use narrative synthesis to analyze the data using quantitative and qualitative methods. Factors associated with postpartum contraception will be organized using the domains and constructs of the PEN-3 Model as a guiding framework. This scoping review will map the research on postpartum contraception among sub-Saharan African immigrant and refugee women living in the US. We expect to identify knowledge gaps, and barriers and facilitators of postpartum contraception in this population. Based on the findings of the review, recommendations will be made for advocacy and program and policy development toward optimizing interpregnancy intervals in sub-Saharan African immigrants living in the US. Review registration Open Science Framework: https://osf.io/s385j.

Genetic association and transferability for urinary albumin-creatinine ratio as a marker of kidney disease in four Sub-Saharan African populations and non-continental individuals of African ancestry.

Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts. Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. Two genome-wide significant (P < 5 × 10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.

Abstract PS18-09: The DARC side of Breast Cancer - DARC, Duffy-null and African ancestry influence in the Triple Negative Breast Cancer tumor microenvironment

Abstract Background. Despite a recent convergence of breast cancer (BC) incidence rates between African American (AA) and European American (EA) women, AA women continue to have ~40% higher mortality rates. BC is a heterogeneous collection of diseases, where African ancestry women are disproportionately burdened with the most aggressive subtype of BC, triple negative BC (TNBC). We have previously reported that the African ancestry-specific Duffy-null allele (FY-) is a risk factor for TNBC diagnoses. FY- is a promoter variant that removes expression of the Duffy Antigen Receptor for Chemokines (DARC/ACKR1), from red blood cells (RBCs). DARC serves as a portal of entry for Plasmodium vivax malaria parasite, and FY- confers immunity, leading to fixation of FY- among Sub-Saharan African populations. DARC is an atypical chemokine receptor that functions to modulate chemokine levels in circulation and tissues to aid immune cell recruitment. DARC is also expressed on breast tumor epithelial cells, however the significance of DARC in the TNBC tumor microenvironment (TME) has not fully been explored. Leveraging our African ancestry enriched International Study for the Center of Breast Cancer Subtypes cohort and in vivo murine models, we employed multi-omics approaches to explore the function of FY- and DARC expression across cell types in the TNBC TME. Genomics. Using transcriptomic data from the TCGA BC cohort, we have previously reported that DARC expression is highly correlated with deconvoluted immune cell abundance using CIBERSORT. To build upon this finding among TNBC patients, we have analyzed RNAseq data from two cohorts of African ancestry women to explore correlation of DARC expression status and immune cell abundance. Among TNBC cases, we report that higher DARC expression was significantly associated with increased immune cell abundance, with increases in B cell, T cell and monocyte populations. Using whole genome sequencing data across 86 African ancestry cases, we are currently investigating germline FY- status with mutational signatures. Circulating biomarkers. Patient plasma was collected prior to surgery, where Luminex multiplex assays were performed to quantify levels of &amp;gt;40 circulating chemokines and cytokines. FY- status has been determined for ~550 patients using single-plex or multiplex PCR genotyping methods from germline saliva DNA. Our univariate analyses show several circulating chemokines, including CCL2, CXCL2, CXCL6 and CXCL11, have significant differences between FY- and non-FY- BC patients. Curation of clinicopathological variables for multivariate analysis is ongoing. Murine models. We crossed C3(1)Tag BC transgenic mice with a DARC knock-out (KO) line to generate mice lacking DARC expression that spontaneously develop tumors in the mammary fat pads. The C3(1)Tag model is reported to have similar gene expression profiles to basal-like TNBC tumors. Tumors were collected at pre-determined time points of 25 and 30 weeks, where DARC KO mice had increased tumor size and tumor burden at 30 weeks. Initial fluorescent staining revealed an increase in immune cell infiltration in the TME of DARC expressing mice compared to DARC KO mice. To further explore this, we employed multiplex staining across a representative cohort of DARC expressing and KO mice at 25 and 30 weeks to capture the specific immune cell populations infiltrating the TME. Conclusions. TNBC tumors have worse prognosis due to lack of targeted therapeutic options. Increased immunogenicity of TNBC tumors, especially among African ancestry women may be driven in part by DARC expression. Characterization of FY- status, in coordination with DARC among other cell types in the TNBC TME could present new opportunities for biomarker and/or therapeutic development to improve prognosis for these underserved populations. Citation Format: Rachel Martini, Stevens Patino, Emma Guyonnet, Brian Stonaker, Isra Elhussein, Julie Sahler, Avery August, Nancy Manley, Rick Kittles, Clayton Yates, Lisa Newman, Melissa Davis. The DARC side of Breast Cancer - DARC, Duffy-null and African ancestry influence in the Triple Negative Breast Cancer tumor microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS18-09.

Review of Genetic and Artificial Intelligence approaches to improving Gestational Diabetes Mellitus Screening and Diagnosis in sub-Saharan Africa.

Background: Adverse outcomes from gestational diabetes mellitus (GDM) in the mother and newborn are well established. Genetic variants may predict GDM and Artificial Intelligence (AI) can potentially assist with improved screening and early identification in lower resource settings. There is limited information on genetic variants associated with GDM in sub-Saharan Africa and the implementation of AI in GDM screening in sub-Saharan Africa is largely unknown. Methods: We reviewed the literature on what is known about genetic predictors of GDM in sub-Saharan African women. We searched PubMed and Google Scholar for single nucleotide polymorphisms (SNPs) involved in GDM predisposition in a sub-Saharan African population. We report on barriers that limit the implementation of AI that could assist with GDM screening and offer possible solutions. Results: In a Black South African cohort, the minor allele of the SNP rs4581569 existing in the PDX1 gene was significantly associated with GDM. We were not able to find any published literature on the implementation of AI to identify women at risk of GDM before second trimester of pregnancy in sub-Saharan Africa. Barriers to successful integration of AI into healthcare systems are broad but solutions exist. Conclusions: More research is needed to identify SNPs associated with GDM in sub-Saharan Africa. The implementation of AI and its applications in the field of healthcare in the sub-Saharan African region is a significant opportunity to positively impact early identification of GDM.

Evaluation of eGFR methods in a sub-Saharan African community-based pediatric population.

Accurate assessment of the estimated glomerular filtration rate (eGFR) plays a pivotal role in the early detection, management, and optimal medication dosing for chronic kidney disease (CKD). However, validation of eGFR, utilizing cystatin C-based equations, is limited in African children and adolescents with CKD. We evaluate the agreement of eGFR equations incorporating both cystatin C and creatinine in this specific population. This community-based study assessed CKD in children (2-15years) using cystatin C and serum creatinine. eGFR agreement with the reference was evaluated with Bland-Altman plots, ROC curves, and Lin's CCC, using the Under-25 serum creatinine-cystatin C equation as the reference standard. Pairwise ROC comparisons assess the statistical differences in estimation equation agreement. Among 666 children (mean age, 7.8 ± 3.8years; 48.6% male), CKD prevalence was 11.6% (95% CI, 9.2-14.2%). Notably, the Chehade equation, using combined biomarkers, aligned best with the reference, displaying the lowest mean deviation (- 0.59; 95% CI, - 1.19 to 0.01), superior agreement (P10, 91.0%; P30, 96.70%), and highest discriminatory power (0.989). In contrast, CKD-EPI 2012 cystatin C had the highest mean deviation (- 35.90) and lowest discriminatory power (0.79). Equations combining creatinine and cystatin C (Schwartz, Chehade, Full Age Spectrum) demonstrated strong positive Lin's CCC with CKiD U25 creatinine-cystatin C, while Bouvet showed a notably weak correlation (Lin's CCC, 0.22). In African children with CKD, the Chehade, CKiD Under 25 creatinine-based equations, and the Full Age Spectrum equations show promise for CKD diagnosis. However, a measured GFR is essential to identifying the most accurate eGFR equation in this population.

Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine

Adverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in SLC22A1, HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.

Association of maternal insulin resistance with neonatal insulin resistance and body composition/size: a prospective cohort study in a sub-Saharan African population.

We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria. We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)]. Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1-10.3), 19.7% (12.9-28.0), 23.1% (15.8-31.8), 10.1% (5.3-17.0), 12.6% (7.2-19.9), 0.8% (0.02-4.5), and 5.0% (1.8-10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (p=0.837), birth weight (p=0.416) or body composition measured with weight-length ratio (p=0.524), but birth weight was independently predicted by maternal weight (p=0.006), body mass index (p=0.001), and parity (p=0.012). In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.

Ethnic and functional differentiation of copy number polymorphisms in Tunisian and HapMap population unveils insights on genome organizational plasticity

Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the “Canary” algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs). In this present work, we investigate the Tunisian population structure using the CNP makers previously identified among Tunisian. The study revealed that Sub-Saharan African populations exhibited the highest diversity with the highest proportions of allelic CNPs. Among all the African populations, Tunisia showed the least diversity. Individual ancestry proportions computed using STRUCTURE analysis revealed a major European component among Tunisians with lesser contribution from Sub-Saharan Africa and Asia. Population structure analysis indicated the genetic proximity with Europeans and noticeable distance from the Sub-Saharan African and East Asian clusters. Seven genes harbouring Tunisian high-frequent CNPs were identified known to be associated with 9 Mendelian diseases and/or phenotypes. Functional annotation of genes under selection highlighted a noteworthy enrichment of biological processes to receptor pathway and activity as well as glutathione metabolism. Additionally, pathways of potential concern for health such as drug metabolism, infectious diseases and cancers exhibited significant enrichment. The distinctive genetic makeup of the Tunisians might have been influenced by various factors including natural selection and genetic drift, resulting in the development of distinct genetic variations playing roles in specific biological processes. Our research provides a justification for focusing on the exclusive genome organization of this population and uncovers previously overlooked elements of the genome.

Investigating the relevance of the advanced activities of daily living tool for the screening and diagnosis of mild cognitive impairment and dementia to the Sub-Saharan African migrant population in Belgium: A qualitative focus group study

Introduction: Early diagnosis of dementia is partly based on the evaluation of the basic (b-), instrumental (i-) and advanced (a-) activities of daily living (ADL). Adapting the item content of assessment tools to maintain relevance, understanding, and equivalence of the items and scales across other groups is pertinent. However, there are limited assessment tools developed on or adapted for use on the growing older Sub-Saharan African (SSA) migrant population in Europe. Focusing on the item content, we evaluated the relevance of the advanced activities of daily living (a-ADL) tool to the older SSA migrant population in Belgium. Method: Two focus group discussions were organized with participants from the SSA community in Gent, Belgium. Relevant, irrelevant, unclear, and new items were identified. The data was analyzed through the inductive method while consensus agreements were used to arrive at refined themes. Results: Out of the 49 items on the tool, both groups unanimously agreed that 15 items were relevant and 23 irrelevant. Thirteen new items were identified, whereas 15 items were considered unclear. Conclusion: Participants agreed the tool was relevant but should be adapted. Verification and validation of these results in a larger SSA older migrant population in Belgium is strongly recommended.

ECCO Global Grant Genetic risk factors for IBD in its emergent phase in sub-Saharan Africa

Abstract Background and Aims Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic, chronic, and frequently disabling inflammatory disorder of the intestines characterized by a dysregulated mucosal immune response. The pathophysiology of the disease remains incompletely understood. Genetic factors affecting disease are under investigation, however, genetic studies in non-European populations are scarce and it is an urgent scientific, social, and ethical requirement that research in under-studied populations is prioritized. The objective of this study is to understand the genetics of IBD in sub-Saharan African ancestry populations and to identify genetic factors that affect pathogenesis of IBD in this region. Methodology A case-control study will be conducted from January 2024 to December 2025. Consecutive eligible subjects with IBD and controls will be invited to take part in the study. Data will be collected through chart review, structured interviews, and collection of saliva samples for genotyping using the H3Africa chip in the first instance. Genome-wide imputation and replication analysis will be done. Single-marker association analyses will be performed using the Cochran Armitage trend and logistic regression test after correction for population structure. We will look at known European ancestry and African American (AA) IBD-associated variants as well as variants that are unique to our populations (we will be able to look at local admixture in the AA population to see if these variants are replicated). Anticipated Impact This study will contribute significantly to knowledge of genetic risk factors for IBD in sub-Saharan Africa. It may also help to identify potential complications of treatments such as thiopurines which have been commonly used in European populations but where experience of use in sub-Saharan Africa is lacking.

Factors associated with frequency of fruit and vegetable consumption among selected sub-Saharan African populations: evidence from the Cardiovascular H3Africa Innovation Resource Project.

Frequent fruit and vegetable consumption is considered a promising dietary behaviour that protects health. However, most existing studies about the factors associated with this phenomenon among Africans are based on single-country reports, apart from one meta-regression combining smaller studies. This study harmonized large datasets and assessed factors associated with the frequency of fruit and vegetable consumption in this population. Individual-level data on sociodemographics, lifestyle and diet from 20 443 participants across five African countries (Burkina Faso, Ghana, Kenya, South Africa and Nigeria), from the Stroke Investigative Research and Educational Network (SIREN) and Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) studies, were harmonized. Total frequency of fruit and vegetable consumption (in portions/week) was classified as 'low' (≤6), 'moderate' (7-14) and 'high' (≥15). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with the total frequency of fruit and vegetable consumption (using 'low' consumption as the reference) were estimated using multinomial regression models. Mean age of participants was 54.3 ± 11.8 years, 10 641 (52.1%) were female, and the median (interquartile range) frequency of total fruit and vegetable consumption was 10.0 (4.0, 21.0) portions/week. Participants with a family history of cardiovascular disease [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.85; 95% CI, 0.78, 0.92)], current smokers [moderate (aOR, 0.83; 95% CI, 0.74, 0.94) and high (aOR, 0.78; 95% CI, 0.69, 0.88)], current alcohol users [moderate (aOR, 0.92; 95% CI, 0.85, 1.00) and high (aOR, 0.82; 95% CI, 0.76, 0.89)] and physically inactive participants [moderate (aOR, 0.85; 95% CI, 0.75, 0.96) and high (aOR, 0.80; 95% CI, 0.70, 0.90)] were less likely to consume fruits and vegetables frequently. Africans with lifestyle risk factors for cardiovascular disease were less likely to consume fruit and vegetables frequently.

The impact of home-based management of malaria on clinical outcomes in sub-Saharan African populations: a systematic review and meta-analysis

BackgroundMalaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the effect of home management of malaria intervention on health outcomes.MethodsIn our systematic review and meta-analysis, six databases (Pubmed, Cochrane CENTRAL, EMBASE, CAB s and Global Health, CINAHL Complete, and BIOSIS) were searched for studies of home management of malaria from inception until November 15, 2023. We included before–after studies, observational studies, and randomised controlled trials of home management intervention delivered in community settings. The primary outcomes were malaria mortality and all-cause mortality. The risk of bias in individual observational studies was assessed using the ROBINS-I tool, whilst randomised controlled trials were judged using a revised Cochrane risk of bias tool and cluster-randomised controlled trials were evaluated using an adapted Cochrane risk of bias tool for cluster-randomised trials. We computed risk ratios with accompanying 95% confidence intervals for health-related outcomes reported in the studies and subsequently pooled the results by using a random-effects model (DerSimonian–Laird method).ResultsWe identified 1203 citations through database and hand searches, from which 56 articles from 47 studies encompassing 234,002 participants were included in the systematic review. All studies were conducted in people living in sub-Saharan Africa and were rated to have a low or moderate risk of bias. Pooled analyses showed that mortality rates due to malaria (RR = 0.40, 95% CI = 0.29–0.54, P = 0.00001, I2 = 0%) and all-cause mortality rates (RR = 0.62, 95% CI = 0.53–0.72, P = 0.00001, I2 = 0%) were significantly lower among participants receiving home management intervention compared to the control group. However, in children under 5 years of age, there was no significant difference in mortality rates before and after implementation of home management of malaria. In terms of secondary outcomes, home management of malaria was associated with a reduction in the risk of febrile episodes (RR = 1.27, 95% CI = 1.09–1.47, P = 0.002, I2 = 97%) and higher effective rates of antimalarial treatments (RR = 2.72, 95% CI = 1.90–3.88, P < 0.00001, I2 = 96%) compared to standard care. Home malaria management combined with intermittent preventive treatment showed a significantly lower incidence risk of malaria than home management intervention that exclusively provided treatment to individuals with febrile illness suggestive of malaria. The risks for adverse events were found to be similar for home management intervention using different antimalarial drugs. Cost-effectiveness findings depicted that home malaria management merited special preferential scale-up.ConclusionsHome management of malaria intervention was associated with significant reductions in malaria mortality and all-cause mortality. The intervention could help decrease health and economic burden attributable to malaria. Further clinical studies are warranted to enable more meaningful interpretations with regard to wide-scale implementation of the intervention, settings of differing transmission intensity, and new antimalarial drugs.

Right atrial strain in a normal adult African population according to age.

Right atrial longitudinal strain (RALS) is a useful parameter to define right atrial (RA) subclinical dysfunction prior to changes in RA dimension and volume. We sought to establish normal values for RALS in a sub-Saharan African population. This was a retrospective, cross-sectional study from 2017 to 2019 of 100 normal individuals. All echocardiographic measurements were done as per the standard guidelines. Mean RALS was 32.7 ± 10.5%. The mean RA volume indexed to body surface area was 19.5 ± 5.7 ml/m2. There was a negative correlation between RALS and age but it was not statistically significant (r = -0.15, p = 0.129). Males had a tendency towards higher RA volume indexed and RALS measurements compared to females (20.8 ± 6.3 and 18.7 ± 5.2 ml/m2, p = 0.07; 34.6 ± 9.6 and 31.4 ± 10.9%, p = 0.141, respectively). Body mass index was an independent predictor of RALS (r = -0.43, p = 0.003). We have provided normative data for RALS in an African population. This study provides a platform for future larger studies on RALS.

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. 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.

Perinatal outcomes in women with lower-range elevated blood pressure and stage 1 hypertension: insights from the Kaya health and demographic surveillance system, Burkina Faso

BackgroundThe impact of lower thresholds for elevated blood pressure (BP) on adverse perinatal outcomes has been poorly explored in sub-Saharan African populations. We aimed to explore the association between lower BP cutoffs (according to the 2017 American College of Cardiology/American Heart Association [ACC/AHA] criteria) and adverse perinatal outcomes in Kaya, Burkina Faso.MethodsThis retrospective cohort study included 2,232 women with singleton pregnancies between February and September 2021. BP was categorized according to the ACC/AHA criteria and applied throughout pregnancy. A multivariable Poisson regression model based on Generalized Estimating Equation with robust standard errors was used to evaluate the association between elevated BP, stage 1 hypertension, and adverse perinatal outcomes, controlling for maternal sociodemographic characteristics, parity, and the number of antenatal consultations, and the results were presented as adjusted risk ratios (aRRs) with corresponding 95% confidence intervals (CIs).ResultsOf the 2,232 women, 1000 (44.8%) were normotensive, 334 (14.9%) had elevated BP, 759 (34.0%) had stage 1 hypertension, and 139 (6.2%) had stage 2 hypertension. There was no significant association between elevated BP and adverse pregnancy outcomes. Compared to normotensive women, women with elevated BP had a 2.05-fold increased risk of delivery via caesarean section (aRR;2.05, 95%CI; 1.08–3.92), while those with stage 1 hypertension had a 1.41-fold increased risk of having low birth weight babies (aRR; 1.41, 95%CI; 1.06–1.86), and a 1.32-fold increased risk of having any maternal or neonatal adverse outcome (aRR; 1.32, 95%CI; 1.02–1.69).ConclusionsOur results suggest that the risk of adverse pregnancy outcomes is not increased with elevated BP. Proactive identification of pregnant women with stage 1 hypertension in Burkina Faso can improve hypertension management through enhanced clinical surveillance.

Sociodemographic and Histological Trends of Breast Lumps in A Sub-Saharan African Population: A Cross-Sectional Study in A Surgical Oncology Department

Objective: The purpose of the study was to present histological profile of both benign breast tumors (BBT) and breast cancer (BC) in our setting and highlight age trends in the occurrence of BBT. Methods: A retrospective cross-sectional study was conducted in the surgical oncology unit of the Dalal Jamm University Hospital from January to July 2023. Dalal Jamm University Hospital is a teaching hospital based in Dakar, Senegal. Results: The median age was 45 years for BC and 31.5 years for BBT. The main histological types of BC were invasive ductal carcinoma (93.2%) and invasive lobular carcinoma (4.5%) whereas it was fibroadenoma (66.6%) for BBT. Fibroadenoma and benign phyllodes tumor was more common in adolescents and under 40 years (p = 0.046) old while fibrocystic changes were more prevalent during perimenopause (p &lt; 0.001). Conclusion: Invasive ductal carcinoma and fibroadenoma are the most common breast tumors in sub-Saharan African setting. Fibroadenoma and benign phyllodes tumor are more prevalent in adolescents and under 40 years while fibrocystic changes occur most within the fourth and fifth decades of life.

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 = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations.

Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa

In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10−11 and 3.74×10−2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.

The genomic footprint of social stratification in admixing American populations.

Cultural and socioeconomic differences stratify human societies and shape their genetic structure beyond the sole effect of geography. Despite mating being limited by sociocultural stratification, most demographic models in population genetics often assume random mating. Taking advantage of the correlation between sociocultural stratification and the proportion of genetic ancestry in admixed populations, we sought to infer the former process in the Americas. To this aim, we define a mating model where the individual proportions of the genome inherited from Native American, European, and sub-Saharan African ancestral populations constrain the mating probabilities through ancestry-related assortative mating and sex bias parameters. We simulate a wide range of admixture scenarios under this model. Then, we train a deep neural network and retrieve good performance in predicting mating parameters from genomic data. Our results show how population stratification, shaped by socially constructed racial and gender hierarchies, has constrained the admixture processes in the Americas since the European colonization and the subsequent Atlantic slave trade.

Use of Race and Ethnicity in Sickle Cell Disease Research

Introduction Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, devastating ischemic pain crises and chronic organ damage, resulting in shortened lifespan. Ethnicity and race are often mentioned in SCD research. Possibly, since SCD is particularly prevalent amongst people who originate from sub-Saharan Africa. In research studies, ethno racial categories (ERCs) are frequently considered confounding variables. However, these ERCs are often large aggregate categories and include individuals with a diversity in phenotype, exposures and genetic make-up. Recent journal submission guidelines urge researchers, when applicable, to declare the relevance of the use of ERCs to the study as well as the modality through which an ERC is determined (e.g. self-identification, country of birth, visual identification by the observer). Providing such detailed information is important because true confounders with a specific feature might distort study results. However, when operationalizing ERCs in SCD research, there exists a risk of reification of already marginalized populations as both a social and a biological group. Therefore, contextualization is essential when deciding to use ERCs in SCD research. This study aims to provide an overview of how ethnicity and race are applied in SCD research. Methods We systematically searched the literature to explore the current practice of ERCs in SCD research across world regions. Embase and Medline were systematically searched in November 2022 for all published articles on SCD published from 2011 onwards. Studies were considered eligible when cases defined as individuals with SCD and controls individuals without SCD. A total of 1,105 articles in SCD research were included. Of these articles, 1,085 were domestic studies and 20 international studies. Statistical tests and models implemented in R included chi-square tests and univariate linear regression. Results In 27% (298/1,085) of all studies, ERC confounder adjustment occurred. This methodological practice was dependent on geographical region the research subjects were sourced from (p&amp;lt;0.05), as made visible in Figure 1. In 175/302 (57%) of studies with a North American study population ERC confounder adjustment took place, as well as in 45% [58/129]) of the studies reporting on a European study population. In contrast, in 6% (14/239) of sub-Saharan African study populations, ERC confounder adjustment was performed (Table 1). Of the twenty international studies, six operationalized ERCs as confounders. In five publications, the control group was sourced from the same country as the SCD cases. One study used a healthy Congolese reference population as a control cohort whilst the SCD patients were from France. ERC confounder adjustment also varied with the biomedical discipline in which the article was published. Compared to Hematological journals, articles published in journals with categories “Medicine, General &amp; Internal medicine” (OR=0.30, 95% CI -1.76 - -0.67, p&amp;lt;0.0001), were less likely to adjust for ERCs as confounders whereas articles in Ophthalmological journals (OR= 3.36, 95% CI 0.27 - 2.23, p=0.01) were more likely to do so. Of the studies that used ERC confounder adjustment, 80% (239/298) did not explain why this was relevant. Furthermore, in 70% (209/298) of these ERC-adjusted studies, it was unclear through which modality ERCs were determined. In the papers that described modalities, 49% (44/89) used ERCs from pre-existing databases, 18%(16/89) used sibling/relative recruitment, 30% (27/89) used self-reporting ERCs and 2% (2/89) used multiple ways to classify ethnicity or race. Moreover, in 28% (83/298) of the ERC-adjusted studies, it was not clear which specific categories were used. Conclusion ERC confounder adjustment is a common occurrence in SCD case-control studies in the United States and Europe. Furthermore, contrary to current author guideline recommendations, reporting on ethnicity and race in SCD studies is frequently inconsistent and incomplete. This confuses the possible relevance of ERCs to the study and inadvertently reinforces reification of these constructs. Moving forward, we recommend the promotion of global guidelines around the use of ERCs in case-control studies to stimulate further research into uncovering specific relevant mechanisms that create differences in health outcomes.