Sally N. Adebamowo

Intakes of magnesium, potassium, and calcium and the risk of stroke among men.

Background Intakes of magnesium, potassium, and calcium have been inversely associated with the incidence of hypertension, a known risk factor for stroke. However, only a few studies have examined intakes of these cations in relation to risk of stroke. Aim The aim of this study was to investigate whether high intake of magnesium, potassium, and calcium is associated with reduced stroke risk among men. Methods We prospectively examined the associations between intakes of magnesium, potassium, and calcium from diet and supplements, and the risk of incident stroke among 42 669 men in the Health Professionals Follow-up Study, aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986. We calculated the hazard ratio of total, ischemic, and haemorrhagic strokes by quintiles of each cation intake, and of a combined dietary score of all three cations, using multivariate Cox proportional hazard models. Results During 24 years of follow-up, 1547 total stroke events were documented. In multivariate analyses, the relative risks and 95% confidence intervals of total stroke for men in the highest vs. lowest quintile were 0·87 (95% confidence interval, 0·74–1·02; P, trend = 0·04) for dietary magnesium, 0·89 (95% confidence interval, 0·76–1·05; P, trend = 0·10) for dietary potassium, and 0·89 (95% confidence interval, 0·75–1·04; P, trend = 0·25) for dietary calcium intake. The relative risk of total stroke for men in the highest vs. lowest quintile was 0·74 (95% confidence interval, 0·59–0·93; P, trend = 0·003) for supplemental magnesium, 0·66 (95% confidence interval, 0·50–0·86; P, trend = 0·002) for supplemental potassium, and 1·01 (95% confidence interval, 0·84–1·20; P, trend = 0·83) for supplemental calcium intake. For total intake (dietary and supplemental), the relative risk of total stroke for men in the highest vs. lowest quintile was 0·83 (95% confidence interval, 0·70–0·99; P, trend = 0·04) for magnesium, 0·88 (95% confidence interval, 0·75–4; P, trend = 6) for potassium, and 3 (95% confidence interval, 79–09; P, trend = 84) for calcium. Men in the highest quintile for a combined dietary score of all three cations had a multivariate relative risk of 0·79 (95% confidence interval, 0·67–0·92; P, trend = 0·008) for total stroke, compared with those in the lowest. Conclusions A diet rich in magnesium, potassium, and calcium may contribute to reduced risk of stroke among men. Because of significant collinearity, the independent contribution of each cation is difficult to define.

Genome-wide analysis identifies an african-specific variant in SEMA4D associated with body mass index.

The prevalence of obesity varies between ethnic groups. No genome‐wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans.

Paucity of HPV-Related Head and Neck Cancers (HNC) in Nigeria

Introduction The burden of HPV-related Head and Neck Cancers (HNC) has been rising in the U.S. and other developed countries but this trend has not been reported in Africa. Objective of study was to evaluate the prevalence of HPV infection in HNC cancer cases seen between 1990 and 2011 at the tertiary health care institutions in Nigeria. Methods We retrieved 149 head and neck cancer formalin fixed, paraffin embedded tumor specimens diagnosed between 1990 and 2011 from four teaching hospitals in Nigeria. One hundred and twenty-three blocks (83%) contained appropriate HNC for analysis while DNA extraction was successful in 60% (90/149). PCR amplification was successful in 33% (49/149) and Linear Array genotyping for HPV was successful in 11% (17/149) of these cases. These were in tumors from the larynx (6), cervical lymph nodes (3), nasal cavity (2), parotid (1), palate (1), maxillary sinus (1) and mandible (1). Two cases were non-specific and none were from the oropharynx. Histologically, 41% (7/17) of the successfully genotyped blocks were squamous cell carcinomas (larynx 6, maxillary sinus 1). Results and Conclusion We were unable to detect HPV in any of the HNC samples in our study. Our result may suggest that there is a low prevalence of HPV-related HNC among the adult population in Nigeria. Our results provide a benchmark to compare future incidence of HPV -related HNC in this community in future. We had significant analytical challenges from possible poor tissue processing and urge that future studies should prospectively collect samples and ensure high quality sample processing.

Mycoplasma hominis and Mycoplasma genitalium in the Vaginal Microbiota and Persistent High-Risk Human Papillomavirus Infection

Background Recent studies have suggested that the vaginal microenvironment plays a role in persistence of high-risk human papillomavirus (hrHPV) infection and thus cervical carcinogenesis. Furthermore, it has been shown that some mycoplasmas are efficient methylators and may facilitate carcinogenesis through methylation of hrHPV and cervical somatic cells. We examined associations between prevalence and persistence of Mycoplasma spp. in the vaginal microbiota, and prevalent as well as persistent hrHPV infections. Methods We examined 194 Nigerian women who were tested for hrHPV infection using SPF25/LiPA10 and we identified Mycoplasma genitalium and Mycoplasma hominis in their vaginal microbiota established by sequencing the V3–V4 hypervariable regions of the 16S rRNA gene. We defined the prevalence of M. genitalium, M. hominis, and hrHPV based on positive result of baseline tests, while persistence was defined as positive results from two consecutive tests. We used exact logistic regression models to estimate associations between Mycoplasma spp. and hrHPV infections. Results The mean (SD) age of the study participants was 38 (8) years, 71% were HIV positive, 30% M. genitalium positive, 45% M. hominis positive, and 40% hrHPV positive at baseline. At follow-up, 16% of the women remained positive for M. genitalium, 30% for M. hominis, and 31% for hrHPV. There was a significant association between persistent M. hominis and persistent hrHPV (OR 8.78, 95% CI 1.49–51.6, p 0.01). Women who were positive for HIV and had persistent M. hominis had threefold increase in the odds of having persistent hrHPV infection (OR 3.28, 95% CI 1.31–8.74, p 0.008), compared to women who were negative for both. Conclusion We found significant association between persistent M. hominis in the vaginal microbiota and persistent hrHPV in this study, but we could not rule out reverse causation. Our findings need to be replicated in larger, longitudinal studies and if confirmed, could have important diagnostic and therapeutic implications.

Building a Platform to Enable NCD Research to Address Population Health in Africa: CVD Working Group Discussion at the Sixth H3Africa Consortium Meeting in Zambia.

Highlights H3Africa CVD-related projects will analyze genomic data for over 50,000 individuals Dataset will contain samples from across various African countries and disease phenotypes H3Africa CVD-related projects will be foundational for translational research

H3Africa: current perspectives

Precision medicine is being enabled in high-income countries by the growing availability of health data, increasing knowledge of the genetic determinants of disease and variation in response to treatment (pharmacogenomics), and the decreasing costs of data generation, which promote routine application of genomic technologies in the health sector. However, there is uncertainty about the feasibility of applying precision medicine approaches in low- and middle-income countries, due to the lack of population-specific knowledge, skills, and resources. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive new research into the genetic and environmental basis for human diseases of relevance to Africans as well as to build capacity for genomic research on the continent. Precision medicine requires this capacity, in addition to reference data on local populations, and skills to analyze and interpret genomic data from the bedside. The H3Africa consortium is collectively processing samples and data for over 70,000 participants across the continent, accompanied in most cases by rich clinical information on a variety of non-communicable and infectious diseases. These projects are increasingly providing novel insights into the genetic basis of diseases in indigenous populations, insights that have the potential to drive the development of new diagnostics and treatments. The consortium has also invested significant resources into establishing high-quality biorepositories in Africa, a bioinformatic network, and a strong training program that has developed skills in genomic data analysis and interpretation among bioinformaticians, wet-lab researchers, and health-care professionals. Here, we describe the current perspectives of the H3Africa consortium and how it can contribute to making precision medicine in Africa a reality.

Common and rare exonic MUC5B variants associated with type 2 diabetes in Han Chinese

Genome-wide association studies have identified over one hundred common genetic risk variants associated with type 2 diabetes (T2D). However, most of the heritability of T2D has not been accounted for. In this study, we investigated the contribution of rare and common variants to T2D susceptibility by analyzing exome array data in 1,908 Han Chinese genotyped with Affymetrix Axiom® Exome Genotyping Arrays. Based on the joint common and rare variants analysis of 57,704 autosomal SNPs within 12,244 genes using Sequence Kernel Association Tests (SKAT), we identified significant associations between T2D and 25 variants (9 rare and 16 common) in MUC5B, p-value 1.01×10−14. This finding was replicated (p = 0.0463) in an independent sample that included 10,401 unrelated individuals. Sixty-six of 1,553 possible haplotypes based on 25 SNPs within MUC5B showed significant association with T2D (Bonferroni corrected p values < 3.2×10−5). The expression level of MUC5B is significantly higher in pancreatic tissues of persons with T2D compared to those without T2D (p-value = 5×10−5). Our findings suggest that dysregulated MUC5B expression may be involved in the pathogenesis of T2D. As a strong candidate gene for T2D, MUC5B may play an important role in the mechanisms underlying T2D etiology and its complications.

Impact of Type 2 Diabetes on Impaired Kidney Function in Sub-Saharan African Populations.

Background Diabetes is a leading risk factor for impaired kidney function, an indicator of chronic kidney disease. The aim of this study was to examine the association between type 2 diabetes (T2D) and impaired kidney function among adults in sub-Saharan Africa (SSA). Methods Participants were enrolled from Ghana, Kenya, and Nigeria. Impaired kidney function was based on an estimated glomerular filtration rate <60 ml/min/1.73 m2. Using logistic regression models, we conducted case–control analyses to estimate the multivariate-adjusted association of T2D and kidney function. Results We used data from 4815 participants for whom the mean (SD) age was 48 (15) years, 41% were male and 46% had T2D. Those with T2D were more likely to have impaired kidney function [13.4% (95% CI: 11.9–14.7)] compared to those without T2D [4.8% (95% CI: 4.0–5.6)], p-value <0.001. The multivariate odds ratio of impaired kidney function among those with type 2 diabetes was 1.50 (95% CI: 1.17–1.91) p-value = 0.001, compared to those without T2D. Also, individuals with T2D who were at least 60 years old, obese, hypertensive or dyslipidemic were more likely to have impaired kidney function compared to those without T2D. Conclusion T2D was associated with 50% increased risk of impaired kidney function in this sample of adults from SSA. Interventions targeted at prevention, early diagnosis, and management of T2D are likely to reduce the burden of kidney disease in SSA.

Genomics of Cardiometabolic Disorders in Sub-Saharan Africa

Sub-Saharan Africa (SSA) is experiencing a growing burden of cardiometabolic disorders, including diabetes, dyslipidemia, hypertension, obesity, coronary heart disease, and stroke. The increasing trends are expected to accelerate as SSA continues to experience economic progress, population growth, and the shift from communicable to noncommunicable diseases. These complex disorders are caused by multiple, potentially interacting, environmental, and genetic factors. While considerable progress has been made in the identification of the sociocultural, demographic, and lifestyle risk factors for cardiometabolic disorders, many genetic factors that underlie individual susceptibility to these diseases remain largely unknown. Although progress in genomic technologies has allowed for systematic characterization of genome-wide genetic diversity in health and disease in European and Asian ancestry populations, conduct of genetic studies in SSA has been underwhelming until recently. Here, we summarize recent understanding of the body of knowledge and highlight research opportunities on the genomics of cardiometabolic disorders in SSA. Published by S. Karger AG, Basel

Test-Retest Reliability of Self-Reported Sexual Behavior History in Urbanized Nigerian Women.

Background Studies assessing risk of sexual behavior and disease are often plagued by questions about the reliability of self-reported sexual behavior. In this study, we evaluated the reliability of self-reported sexual history among urbanized women in a prospective study of cervical HPV infections in Nigeria. Methods We examined test–retest reliability of sexual practices using questionnaires administered at study entry and at follow-up visits. We used the root mean squared approach to calculate within-person coefficient of variation (CVw) and calculated the intra-class correlation coefficient (ICC) using two way, mixed effects models for continuous variables and (κ^) statistics for discrete variables. To evaluate the potential predictors of reliability, we used linear regression and log binomial regression models for the continuous and categorical variables, respectively. Results We found that self-reported sexual history was generally reliable, with overall ICC ranging from 0.7 to 0.9; however, the reliability varied by nature of sexual behavior evaluated. Frequency reports of non-vaginal sex (agreement = 63.9%, 95% CI: 47.5–77.6%) were more reliable than those of vaginal sex (agreement = 59.1%, 95% CI: 55.2–62.8%). Reports of time-invariant behaviors were also more reliable than frequency reports. The CVw for age at sexual debut was 10.7 (95% CI: 10.6–10.7) compared with the CVw for lifetime number of vaginal sex partners, which was 35.2 (95% CI: 35.1–35.3). The test–retest interval was an important predictor of reliability of responses, with longer intervals resulting in increased inconsistency (average change in unreliability for each 1 month increase = 0.04, 95% CI = 0.07–0.38, p = 0.005). Conclusion Our findings suggest that overall, the self-reported sexual history among urbanized Nigeran women is reliable.