Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans

\ua9 The Author(s) 2024. Background: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans. Methods: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation. Results: We observed genome-wide significant (P-value < 5.0E−8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E−6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E−6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E−6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping. Conclusions: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke’s risk prediction and development of new targeted interventions to prevent or treat stroke

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa

Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery of 187 Novel Risk Variants

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Pattern of waning of maternal antibodies against newcastle disease of chicks from selected hatcheries in Kumasi, Ghana.

This study was conducted to measure and compare the rate at which maternal antibodies against Newcastle Disease (ND) wane in chicks from some selected hatcheries in Kumasi, Ghana. Sera from 150 unvaccinated cockerels collected from three hatcheries (A, B, C) were screened using standard methods of heamagglutination inhibition technique. Two separate vaccination schedules against ND were employed in advising poultry farmers at the Regional Veterinary Laboratory were compared for their suitability. Descriptive statistics was employed. All the chicks from the three hatcheries had maternal antibodies against ND at day-1 and that the maternal antibodies lasted till day-21. Hatchery A had the highest maternal antibody titre of 9.97 GMT at day-1, followed by B with 7.84 GMT and C having the lowest GMT of 6.70. Based on the vaccination schedule, schedule (I) which puts the first Newcastle vaccination at 8 days old (week 1) would not be favourable for any of the chicks that were obtained from the three hatcheries due to the presence of protective maternal antibody levels (4.0 GMT) in sera obtained from chicks during the first week of age. Schedule (II) which puts the first ND vaccination at day-15 favored hatcheries A and C. This is because the MAb titres of chicks from hatcheries A and C decayed below the protective titres after day- 14. This study represents the first report on waning pattern of Newcastle disease specific MAb in chicks in Ghana and it also showed that vaccination schedule should take cognizance of MAb evaluation for the control incessant ND outbreaks.Keywords: Decay, Maternal antibodies (MAb), Newcastle Disease (ND), Vaccination schedule, Ghan

Unemployment, personality traits, and the use of Facebook does online social support influence continuous use?

Abstract Different personality traits respond differently to unfavourable life situations. Unemployment can have several negative social, economic, and domestic consequences. Many people use social media for a variety of reasons. The aim of this study is to examine the way different personality traits respond to Facebook in the period of unemployment. Data was obtained from 3,002 unemployed respondents in Nigeria. The study used regression model to analyse the data. Among the five personality traits, results indicated that the relationship between neuroticism and online social support was negative. However, the relationship between online social support and satisfaction was positive. The study highlights several theoretical and practical implications

Unemployment, Personality Traits, and the Use of Facebook

Different personality traits respond differently to unfavourable life situations. Unemployment can have several negative social, economic, and domestic consequences. Many people use social media for a variety of reasons. The aim of this study is to examine the way different personality traits respond to Facebook in the period of unemployment. Data was obtained from 3,002 unemployed respondents in Nigeria. The study used regression model to analyse the data. Among the five personality traits, results indicated that the relationship between neuroticism and online social support was negative. However, the relationship between online social support and satisfaction was positive. The study highlights several theoretical and practical implications.peerReviewe

Afro Middle East Asian symposium on cancer cooperation

This manuscript captures the discussion and recommendations that came out of a special Afro Asian symposium involving 13 countries. Unmet needs and cost-effective solutions with special emphasis on training form the backbone of practical next steps

Investigating students’ perception towards the use of social media for computing education in Nigeria

Abstract This study examined the use of a social media platform — WhatsApp — by computer science students for learning computing education in the context of a Nigerian education institution. Nowadays, a large community of students in higher education institutions has embraced the WhatsApp platform for social interactions which makes it a useful tool in education. In this study, students formed three closed groups, and each group had a specific computing topic they discussed. Their discussions were in the form of posting questions, providing answers to questions, or expressing knowledge on the group topic. A questionnaire was used to collect data from the participants regarding their experiences. We conducted a descriptive analysis of the students’ learning outcomes. The results show that the use of social media contributes positively to students’ learning achievement, and they are motivated to acquire more knowledge about different computing topics