Purpose
A region of chromosome 22 which includes
APOL1
and
MYH9
genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal ...segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.
Methods
To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on
APOL1
(
n
= 4) and
MYH9
(
n
= 5) genes.
Results
We observed significantly strong associations with previously reported
APOL1
variants rs73885319 and rs60910145, and their two-allele “G1” haplotype (
P
< 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the
MYH9
variants or haplotypes after accounting for multiple testing in our sample.
Conclusions
In conclusion,
APOL1
risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on
APOL1/MYH9
variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.
High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and is more prevalent in African Americans as compared to other US groups. Although large, population-based ...genome-wide association studies (GWAS) have identified over 300 common polymorphisms modulating inter-individual BP variation, largely in European ancestry subjects, most of them do not localize to regions previously identified through family-based linkage studies. This discrepancy has remained unexplained despite the statistical power differences between current GWAS and prior linkage studies. To address this issue, we performed genome-wide linkage analysis of BP traits in African-American families from the Family Blood Pressure Program (FBPP) and genotyped on the Illumina Human Exome BeadChip v1.1. We identified a genomic region on chromosome 1q31 with LOD score 3.8 for pulse pressure (PP), a region we previously implicated in DBP studies of European ancestry families. Although no reported GWAS variants map to this region, combined linkage and association analysis of PP identified 81 rare and low frequency exonic variants accounting for the linkage evidence. Replication analysis in eight independent African ancestry cohorts (N = 16,968) supports this specific association with PP (P = 0.0509). Additional association and network analyses identified multiple potential candidate genes in this region expressed in multiple tissues and with a strong biological support for a role in BP. In conclusion, multiple genes and rare variants on 1q31 contribute to PP variation. Beyond producing new insights into PP, we demonstrate how family-based linkage and association studies can implicate specific rare and low frequency variants for complex traits.
Genome-wide association (GWA) studies have identified common variants that are associated with a variety of traits and diseases, but most studies have been performed in European-derived populations. ...Here, we describe the first genome-wide analyses of imputed genotype and copy number variants (CNVs) for anthropometric measures in African-derived populations: 1188 Nigerians from Igbo-Ora and Ibadan, Nigeria, and 743 African-Americans from Maywood, IL. To improve the reach of our study, we used imputation to estimate genotypes at ∼2.1 million single-nucleotide polymorphisms (SNPs) and also tested CNVs for association. No SNPs or common CNVs reached a genome-wide significance level for association with height or body mass index (BMI), and the best signals from a meta-analysis of the two cohorts did not replicate in ∼3700 African-Americans and Jamaicans. However, several loci previously confirmed in European populations showed evidence of replication in our GWA panel of African-derived populations, including variants near IHH and DLEU7 for height and MC4R for BMI. Analysis of global burden of rare CNVs suggested that lean individuals possess greater total burden of CNVs, but this finding was not supported in an independent European population. Our results suggest that there are not multiple loci with strong effects on anthropometric traits in African-derived populations and that sample sizes comparable to those needed in European GWA studies will be required to identify replicable associations. Meta-analysis of this data set with additional studies in African-ancestry populations will be helpful to improve power to detect novel associations.
Background. Breast cancer is the leading cause of cancer-related mortality among women in Ghana. Data are limited on the predictors of poor outcomes in breast cancer patients in low-income countries; ...however, prolonged waiting time has been implicated. Among breast cancer patients who received treatment at Korle Bu Teaching Hospital, this study evaluated duration and factors that influenced waiting time from first presentation to start of definitive treatment. Method. We conducted a hospital-based retrospective study of 205 breast cancer patients starting definitive treatment at Korle Bu Teaching Hospital between May and December 2013. We used descriptive statistics to summarize patient characteristics. Mann–Whitney U and Kruskal–Wallis tests and Spearman rank correlation were performed to examine the patients, health system, and health worker factors associated with median waiting time. Poisson regression was used to examine the determinants of waiting time. Results. The mean age of the patients was 51.1 ± 11.8 years. The median waiting time was 5 weeks. The determinants of waiting time were level of education, age, income, marital status, ethnicity, disease stage, health insurance status, study sites, time interval between when biopsy was requested and when results were received and receipt of adequate information from health workers. Conclusion. A prolonged waiting time to treatment occurs for breast cancer patients in Ghana, particularly for older patients, those with minimal or no education, with lower income, single patients, those with late disease, those who are insured, and who did not receive adequate information from the health workers. Time to obtain biopsy reports should be shortened. Patients and providers need education on timely treatment to improve prognosis.
Sex disparity in hypertension prevalence is well established in developed nations; however, there is paucity of data on the distribution of hypertension prevalence between the sexes in developing ...countries. Therefore, the authors examined sex differences in hypertension prevalence and cardiovascular risk factors in a sample of 352 healthy hospital workers in Nigeria. The mean ages of the men and women were 37.2±7.9 and 44.7±9.1 years, respectively. Thirty‐five percent of participants were hypertensive, with 54% on treatment and 70% with controlled blood pressure. Men had a higher prevalence of hypertension (38.4% vs 33.0%) and prehypertension (37.6% vs 29.7%). Women had significantly higher odds of developing hypertension and of being on treatment. Mean blood pressure and fasting plasma glucose values were higher in men, while women were more often older, obese, and dyslipidemic and had a lower mean estimated glomerular filtration rate (P<.0001). These findings indicate sex disparity in blood pressure among hospital employees. Sex‐focused management of hypertension is therefore advocated for hospital employees.
Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure (BP), BMI, and ...high-density lipoprotein cholesterol (HDL-C).
This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, wherein ancestry association evidence for hypertension, BMI, or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1733 unrelated African-Americans from the National Heart, Lung and Blood Institute's Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, SBP, DBP, BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age, sex, local marker ancestry, and BMI, as applicable. An individual's African ancestry estimated from 2507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification.
CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (P < 0.0006). F2RL1 (rs631465) on chromosome 5 was associated with BMI (P = 0.0005). Local ancestry in these regions was associated with the respective traits as well.
This study suggests that CXADR and F2RL1 likely play important roles in BP and obesity variation, respectively; and these findings are consistent with those of other studies, so replication and functional analyses are necessary.
Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle ...cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs, and challenges. A major component of the workshop was new approaches to harness SCDO to harmonize data elements used by different studies. This was facilitated by a web-based platform onto which participants uploaded data elements from previous or ongoing SCD-relevant research studies before the workshop, making multisite collaborative research studies based on existing SCD data possible, including multisite cohort, SCD global clinical trials, and SCD community engagement approaches. Trainees presented proposals for systematic literature reviews in key SCD research areas. This expert review emphasizes potential and prospects of SCDO-enabled data standards and harmonization to facilitate large-scale global SCD collaborative initiatives. As the fields of public and global health continue to broaden toward planetary health, the SCDO is well poised to play a prominent role to decipher SCD pathophysiology further, and co-design diagnostics and therapeutics innovation in the field.
Background: Circadian variation in blood pressure (BP) has been shown to determine cardiovascular events in people with chronic kidney diseases (CKDs). Studies aimed at elucidating the relationship ...between diurnal variation in BP and cardiovascular disease have yielded conflicting results, and very few of these studies have been conducted on CKD patients in Sub-Saharan Africa, hence the need for this study. Subjects and Methods: Eighty-five adult participants comprising 54 patients with CKD (36 males and 18 females) and 31 hypertensive patients (16 males and 15 females) free of CKD were recruited for 24 h ambulatory BP monitoring and cardiovascular risk factor assessment. Results: Patients with CKD had a higher mean clinic systolic BP (159.8 ± 28.6 vs. 147.9 ± 19.0 mmHg, P = 0.049) and reduced estimated glomerular filtration rate (19.2 ± 18.6 vs. 106.2 ± 30.6, P < 0.0001) when compared with hypertensives free of CKD. The mean 24 h ambulatory SBP (135.9 ± 28.5 vs. 120.3 ± 11.8 mmHg, P = 0.007), diastolic BP (82.6 ± 18.1 vs. 74.8 ± 9.0 mmHg, P = 0.034) and mean arterial pressure (100.9 ± 21.2 vs. 90.6 ± 10.2 mmHg, P = 0.018) were higher amongst CKD patients. Compared with hypertensive without CKD, daytime hypertension (58.9% vs. 21.4, P = 0.001), nocturnal hypertension (80.4% vs. 50.0%, P = 0.004) and non-dippers (92.0% vs. 73.1%, P = 0.026) were commoner in people with CKD. White coat effect was more common amongst hypertensives without CKD (74.2% vs. 38.0%, P = 0.002). The mean left atrial diameter and left ventricular mass index were higher in CKD group. Conclusion: This study highlights the high prevalence of varied phenotypes in circadian rhythm amongst CKD patients. Ambulatory blood pressure monitoring may be useful for early risk stratification of CKD patients. Large longitudinal study is needed to assess the prognostic implication of the findings.
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