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1.
BMC Public Health ; 24(1): 1739, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951824

ABSTRACT

BACKGROUND: Providing children with the opportunity to learn about nutrition is critical in helping them establish a healthy lifestyle and eating behaviours that would remain with them till adulthood. We determined the effect of a school-based food and nutrition education (SFNE) intervention on the nutrition-related knowledge, attitudes, dietary habits, physical activity levels and the anthropometric indices (BMI-for-age z scores, %Body fat and waist circumference) of school-age children in northern Ghana. METHODS: Following a controlled before-and-after study design, we recruited school-age children in primary 4 and 5 from public and private schools and assigned them non-randomly to intervention and control groups (4 schools total). A SFNE intervention called 'Eat Healthy, Grow Healthy (EHGH)' was implemented in intervention schools. Components of the intervention included children, teachers, school officials, and the school environment. Nutrition education didactic sessions, active discussions, nutrition games, charades, art work, and physical activity sessions were among the teaching and learning activities implemented. At 0 and 6 months, primary (anthropometry) and secondary (fruit, vegetable, and breakfast consumption) outcomes were obtained. RESULTS: Mean BMI-for-age z-scores did not differ significantly between intervention and control groups (F1,261 = 0.45, P = 0.503, η2 = 0.01). However, significantly greater nutrition-related knowledge scores were recorded in the intervention group than in the control group at post-intervention (M = 6.07 SD = 2.17 vs. M = 5.22 SD = 1.92; p = 0.002). Mean number of days intervention children consumed fruits differed across time (F1, 263 = 33.04, p = 0.002, η2 = 0.04) but not between the control and intervention groups (F1, 263 = 0.28, p = 0.60, η2 = 0.00). CONCLUSIONS: The EHGH intervention had positive effects on the nutrition-related knowledge and the consumption of fruits among children although it did not impact their anthropometric indices.


Subject(s)
Fruit , Health Education , Health Knowledge, Attitudes, Practice , School Health Services , Humans , Ghana , Female , Male , Child , Feeding Behavior , Schools
2.
PLoS One ; 19(4): e0295293, 2024.
Article in English | MEDLINE | ID: mdl-38598554

ABSTRACT

RiSE study aims to evaluate a race-based stress-reduction intervention as an effective strategy to improve coping and decrease stress-related symptoms, inflammatory burden, and modify DNA methylation of stress response-related genes in older AA women. This article will describe genomic analytic methods to be utilized in this longitudinal, randomized clinical trial of older adult AA women in Chicago and NYC that examines the effect of the RiSE intervention on DNAm pre- and post-intervention, and its overall influence on inflammatory burden. Salivary DNAm will be measured at baseline and 6 months following the intervention, using the Oragene-DNA kit. Measures of perceived stress, depressive symptoms, fatigue, sleep, inflammatory burden, and coping strategies will be assessed at 4 time points including at baseline, 4 weeks, 8 weeks, and 6 months. Genomic data analysis will include the use of pre-processed and quality-controlled methylation data expressed as beta (ß) values. Association analyses will be performed to detect differentially methylated sites on the targeted candidate genes between the intervention and non-intervention groups using the Δß (changes in methylation) with adjustment for age, health behaviors, early life adversity, hybridization batch, and top principal components of the probes as covariates. To account for multiple testing, we will use FDR adjustment with a corrected p-value of <0.05 regarded as statistically significant. To assess the relationship between inflammatory burden and Δß among the study samples, we will repeat association analyses with the inclusion of individual inflammation protein measures. ANCOVA will be used because it is more statistically powerful to detect differences.


Subject(s)
Black or African American , DNA Methylation , Aged , Female , Humans , Black or African American/genetics , Chicago , Genomics , Inflammation/genetics , New York City , Randomized Controlled Trials as Topic
3.
Res Sq ; 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37790348

ABSTRACT

Background: More than half of patients with hypertension in sub-Saharan African do not achieve blood pressure control. This study determined the effect of mobile health technology on systolic blood pressure reduction and blood pressure (BP) control among patients with hypertension in Nigeria and Ghana. Methods: A randomised control trial of 225 adults with hypertension attending two General/Medical Outpatient Clinics each in Nigeria and Ghana was randomized into intervention (n = 116) and control (n = 109) arm respectively. Patients in the intervention arm received messages twice weekly from a mobile app for six months in addition to the usual care while the control arm received usual care only. The study outcomes were systolic blood pressure (SBP) reduction and blood pressure control at six months, while the secondary outcome was medication adherence at six months. Data were collected at 0 and 6 months, it was analysed using SPSS-21 software at a significance level of p < 0.05. Binary logistic regression was used to generate the predictors of good blood pressure control. Results: The mean age for the control and intervention were 60.2 ± 13.5 and 62.6 ± 10.8 years respectively; p-value = 0.300. The intervention group had greater reductions in SBP (-18.7mmHg vs -3.9mmHg; p < 0.001) and greater BP control rate (44.3% vs 24.8%; p-value 0.002). Conclusions: The mobile health intervention resulted in significant SBP reduction rate and improvement in BP control rate in the 6th month. However, improvement in adherence level in the 3rd month and was not sustained in the 6th month. The addition of mobile health technology may be extended for use in the national hypertension control plan. Female gender, formal education and being in the intervention arm were predictors of blood pressure control.

4.
Kidney Int Rep ; 8(3): 658-666, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36938080

ABSTRACT

Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD); however, the burden of cardiovascular risk factors in patients with CKD in Africa is not well characterized. We determined the prevalence of selected cardiovascular risk factors, and association with CKD in the Human Heredity for Health in Africa Kidney Disease Research Network study. Methods: We recruited patients with and without CKD in Ghana and Nigeria. CKD was defined as estimated glomerular filtration rate of <60 ml/min per 1.73 m2 and/or albuminuria as albumin-to-creatinine ratio <3.0 mg/mmol (<30 mg/g) for ≥3 months. We assessed self-reported (physician-diagnosis and/or use of medication) hypertension, diabetes, and elevated cholesterol; and self-reported smoking as cardiovascular risk factors. Association between the risk factors and CKD was determined by multivariate logistic regression. Results: We enrolled 8396 participants (cases with CKD, 3956), with 56% females. The mean age (45.5 ± 15.1 years) did not differ between patients and control group. The prevalence of hypertension (59%), diabetes (20%), and elevated cholesterol (9.9%), was higher in CKD patients than in the control participants (P < 0.001). Prevalence of risk factors was higher in Ghana than in Nigeria. Hypertension (adjusted odds ratio [aOR] = 1.69 [1.43-2.01, P < 0.001]), elevated cholesterol (aOR = 2.0 [1.39-2.86, P < 0.001]), age >50 years, and body mass index (BMI) <18.5 kg/m2 were independently associated with CKD. The association of diabetes and smoking with CKD was modified by other risk factors. Conclusion: Cardiovascular risk factors are prevalent in middle-aged adult patients with CKD in Ghana and Nigeria, with higher proportions in Ghana than in Nigeria. Hypertension, elevated cholesterol, and underweight were independently associated with CKD.

5.
SAGE Open Med ; 11: 20503121231152324, 2023.
Article in English | MEDLINE | ID: mdl-36741928

ABSTRACT

Objectives: This study sought to assess the current impact of health insurance coverage on medication adherence and blood pressure control of patients being managed for hypertension in Ghana and Nigeria. Methods: The study was a prospective study among 109 patients with hypertension in two health facilities with similar population dynamics in Ghana and Nigeria. Patients were systematically selected, categorized as having health insurance coverage or not, and followed up monthly for 6 months. The outcome variables (medication adherence and blood pressure control) were then measured and compared at 6 months. Analysis was done using Stata with level of significance set at p ⩽ 0.05. Results: There was a 90% insurance coverage among participants from Ghana compared to 15% from Nigeria. National Health Insurance Authority enrolees in both countries had better blood pressure control and medication adherence compared to non-enrolees (adjusted odds ratio = 2.6 and 4.5, respectively). Conclusion: National Health Insurance Authority enrolment was found to be poor among respondents in Nigeria compared to Ghana. Enrolment into the National health financing schemes in both countries led to better blood pressure control and medication adherence among patients with hypertension at primary health facilities. There is therefore the need for system strengthening to improve their sustainability.

6.
Afr Health Sci ; 22(1): 344-351, 2022 Mar.
Article in English | MEDLINE | ID: mdl-36032486

ABSTRACT

Background: Excess cardiovascular burden in patients with chronic kidney disease (CKD) has been attributed to the occurrence of CKD-Mineral Bone Disease (CKD - MBD). This study aimed to determine the spectrum of CKD-MBD among Nigerians with CKD using Fibroblast Growth Factor 23 (FGF 23) and intact Parathyroid Hormone (iPTH). Methods: Cross sectional survey of 105 patients with non-diabetic CKD and 104 controls. Information obtained were demographics, aetiology of CKD, features of CKD-MBD. Serum iPTH and FGF 23 were assayed. Results: The mean ages were 48.7±15.3 vs 48.6±17.4 years while 54.7% and 45.2% were males for cases and controls, respectively. The mean plasma FGF 23 (392.8±35.3 vs 133.8±22.7 RU/mL and plasma iPTH (289±25.6 vs 118±10.8 ng/L, respectively. The frequency of elevated FGF 23 (45.7% vs 24.0%, p<0.01) and abnormal iPTH (53.3% vs 14.1%, p- 0.01) were higher in cases. The prevalence of MBD were (59.0% vs 14.4%, p<0.01) in cases and controls while dialysis status OR 2.94, 95% CI (1.2803-5.3645), and elevated FGF 23 OR, 1.87, 95% CI (1.1782-5.4291) were associated with CKD-MBD. Conclusion: The study demonstrated high prevalence of CKD-MBD among patients with non-diabetic CKD while FGF23 and iPTH were useful assays in the diagnosis of CKD-MBD among Nigerians with CKD.


Subject(s)
Chronic Kidney Disease-Mineral and Bone Disorder , Renal Insufficiency, Chronic , Adult , Aged , Biomarkers , Cross-Sectional Studies , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Humans , Male , Middle Aged , Minerals , Nigeria , Parathyroid Hormone
7.
Commun Biol ; 5(1): 580, 2022 06 13.
Article in English | MEDLINE | ID: mdl-35697829

ABSTRACT

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.


Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Creatinine , Diabetic Nephropathies/genetics , Genome-Wide Association Study , Glomerular Filtration Rate/genetics , Humans , Kidney
8.
Kidney Int ; 102(3): 624-639, 2022 09.
Article in English | MEDLINE | ID: mdl-35716955

ABSTRACT

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.


Subject(s)
N-Acetylgalactosaminyltransferases , Renal Insufficiency, Chronic , Renal Insufficiency , Cross-Sectional Studies , Genetic Loci , Genome-Wide Association Study , Glomerular Filtration Rate/genetics , Humans , Kidney , Longitudinal Studies , N-Acetylgalactosaminyltransferases/genetics , Renal Insufficiency/genetics
10.
Implement Sci Commun ; 3(1): 43, 2022 Apr 15.
Article in English | MEDLINE | ID: mdl-35428342

ABSTRACT

BACKGROUND: Evidence-based task-strengthening strategies for hypertension (HTN) control (TASSH) are not readily available for patients living with HIV in sub-Saharan Africa where the dual burden of HTN and HIV remains high. We are conducting a cluster randomized controlled trial comparing the effectiveness of practice facilitation versus a self-directed control (i.e., receipt of TASSH with no practice facilitation) in reducing blood pressure and increasing the adoption of task-strengthening strategies for HTN control within HIV clinics in Nigeria. Prior to implementing the trial, we conducted formative research to identify factors that may influence the integration of TASSH within HIV clinics in Nigeria. METHODS: This mixed-methods study was conducted with purposively selected healthcare providers at 29 HIV clinics, followed by a 1-day stakeholder meeting with 19 representatives of HIV clinics. We collected quantitative practice assessment data using two instruments: (a) an adapted Service Availability and Readiness Assessment (SARA) tool to assess the capacity of the clinic to manage NCDs and (b) Implementation Climate Scale to assess the degree to which there is a strategic organizational climate supportive of the evidence-based practice implementation. The quantitative data were analyzed using descriptive statistics and measures of scale reliability. We also used the Consolidated Framework for Implementation Research (CFIR), to thematically analyze qualitative data generated and relevant to the aims of this study. RESULTS: Across the 29 clinics surveyed, the focus on TASSH (mean=1.77 (SD=0.59)) and educational support (mean=1.32 (SD=0.68)) subscales demonstrated the highest mean score, with good-excellent internal consistency reliability (Cronbach's alphas ranging from 0.84 to 0.96). Within the five CFIR domains explored, the major facilitators of the intervention included relative advantage of TASSH compared to current practice, compatibility with clinic organizational structures, support of patients' needs, and intervention alignment with national guidelines. Barriers included the perceived complexity of TASSH, weak referral network and patient tracking mechanism within the clinics, and limited resources and diagnostic equipment for HTN. CONCLUSION: Optimizing healthcare workers' implementation of evidence-based TASSH within HIV clinics requires attention to both the implementation climate and contextual factors likely to influence adoption and long-term sustainability. These findings have implications for the development of effective practice facilitation strategies to further improve the delivery and integration of TASSH within HIV clinics in Nigeria. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04704336.

11.
Implement Sci ; 16(1): 96, 2021 11 16.
Article in English | MEDLINE | ID: mdl-34789277

ABSTRACT

BACKGROUND: In regions with weak healthcare systems, critical shortages of the healthcare workforce, and increasing prevalence of dual disease burdens, there is an urgent need for the implementation of proven effective interventions and strategies to address these challenges. Our mixed-methods hybrid type II effectiveness-implementation study is designed to fill this evidence-to-practice gap. This study protocol describes a cluster randomized controlled trial which evaluates the effectiveness of an implementation strategy, practice facilitation (PF), on the integration, adoption, and sustainability of a task-strengthening strategy for hypertension control (TASSH) intervention within primary healthcare centers (PHCs) in Lagos State, Nigeria. DESIGN: Guided by the Consolidated Framework for Implementation Research (CFIR) and the Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM), this study tests the impact of a proven effective implementation strategy to integrate hypertension management into the HIV care cascade, across 30 PHCs. The study will be conducted in three phases: (1) a pre-implementation phase that will use CFIR to develop a tailored PF intervention for integrating TASSH into HIV clinics; (2) an implementation phase that will use RE-AIM to compare the clinical effectiveness of PF vs. a self-directed condition (receipt of information on TASSH without PF) on BP reduction; and (3) a post-implementation phase that will use RE-AIM to evaluate the effect of PF vs. self-directed condition on adoption and sustainability of TASSH. The PF intervention components comprise (a) an advisory board to provide leadership support for implementing TASSH in PHCs; (b) training of the HIV nurses on TASSH protocol; and (c) training of practice facilitators, who will serve as coaches, provide support, and performance feedback to the HIV nurses. DISCUSSION: This study is one of few, if any trials, to evaluate the impact of an implementation strategy for integrating hypertension management into HIV care, on clinical and implementation outcomes. Findings from this study will advance implementation science research on the effectiveness of tailoring an implementation strategy for the integration of an evidence-based, system-level hypertension control intervention into HIV care and treatment. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04704336 ). Registered on 11 January 2021.


Subject(s)
HIV Infections , Hypertension , HIV Infections/therapy , Humans , Hypertension/therapy , Implementation Science , Nigeria , Primary Health Care , Randomized Controlled Trials as Topic
12.
Blood Cells Mol Dis ; 91: 102590, 2021 11.
Article in English | MEDLINE | ID: mdl-34256313

ABSTRACT

BACKGROUND: There is no reliable marker for detecting early renal disease in early children with sickle cell disease (SCD). Estimation of glomerular filtration rate (eGFR) as derived from the height/plasma creatinine formula is dependent on the accuracy of the creatinine analytical method used. The aim of this study was to evaluate different equations for eGFR. METHODS: Children aged 5-16 years recruited. mGFR was obtained using plasma disappearance of Inutest/Iohexol, serum creatinine (SCr) was measured either by standard laboratory method or by tandem mass spectrometry (MSMS). Estimated GFR was then calculated either by "Bedside Schwartz method" or by the full-age spectrum (FAS) equation. FINDINGS: A total of 79 patients (mean age 9.8 ± 4.0 years). A revised eGFR constant was calculated for Schwartz equation from the slope of the plot of height/plasma creatinine versus mGFR. Mean values for mGFR (132.7 ± 32.1 ml/min/1.73m2) and eGFR methods compared: eGFR from standard SCr was significantly higher (144.2 ± 37.3 ml/min/1.73m2, p = 0.008). The MSMS eGFR showed the lowest SD (SD = 27.5), while both FAS eGFR and FAS-height eGFR showed the highest correlation coefficient (r = 0.67). INTERPRETATION: eGFR calculation based on height and SCr determined with MSMS traceable creatinine is more reliable than Schwartz formula using jaffe/enzymatic methods in SCD children.


Subject(s)
Anemia, Sickle Cell/physiopathology , Glomerular Filtration Rate , Kidney/physiopathology , Adolescent , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/urine , Child , Child, Preschool , Female , Humans , Kidney Function Tests , Male , Pilot Projects , Reproducibility of Results
13.
Mol Psychiatry ; 26(6): 2111-2125, 2021 06.
Article in English | MEDLINE | ID: mdl-32372009

ABSTRACT

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.


Subject(s)
Genome-Wide Association Study , Hypertension , Blood Pressure/genetics , Epistasis, Genetic , Genetic Loci , Humans , Hypertension/genetics , Polymorphism, Single Nucleotide
14.
Br J Haematol ; 193(3): 628-632, 2021 05.
Article in English | MEDLINE | ID: mdl-33216373

ABSTRACT

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit ß (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy.


Subject(s)
Adaptor Proteins, Signal Transducing , Anemia, Sickle Cell , Apolipoprotein A-I , Cell Movement/genetics , Down-Regulation , Gene Regulatory Networks , Renal Insufficiency, Chronic , Up-Regulation , Adaptor Proteins, Signal Transducing/biosynthesis , Adaptor Proteins, Signal Transducing/genetics , Adult , Albuminuria/genetics , Albuminuria/metabolism , Anemia, Sickle Cell/genetics , Anemia, Sickle Cell/metabolism , Animals , Apolipoprotein A-I/biosynthesis , Apolipoprotein A-I/genetics , Female , Humans , Male , Mice , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/metabolism
15.
Kidney Int ; 99(4): 926-939, 2021 04.
Article in English | MEDLINE | ID: mdl-33137338

ABSTRACT

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.


Subject(s)
Genome-Wide Association Study , Kidney , AMP-Activated Protein Kinases , Creatinine , Glomerular Filtration Rate/genetics , Humans , Protein Disulfide-Isomerases , United Kingdom
16.
OMICS ; 24(10): 559-567, 2020 10.
Article in English | MEDLINE | ID: mdl-33021900

ABSTRACT

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.


Subject(s)
Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/etiology , Anemia, Sickle Cell/therapy , Anemia, Sickle Cell/epidemiology , Animals , Disease Management , Disease Susceptibility , Humans , Research
17.
J Am Heart Assoc ; 9(17): e017039, 2020 09.
Article in English | MEDLINE | ID: mdl-32851884

ABSTRACT

Background APOL1 high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants' associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. Methods and Results Using linear regression, we examined cross-sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000-2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with APOL1 high- versus low-risk genotypes (P>0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between-group differences of -0.20, -0.14, and -0.25, respectively; P>0.05 for all). Conclusions Among Black participants in MESA, APOL1 high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.


Subject(s)
Apolipoprotein L1/genetics , Arteries/physiopathology , Atherosclerosis/ethnology , Blood Pressure/genetics , Endothelium, Vascular/physiopathology , Aged , Atherosclerosis/genetics , Case-Control Studies , Cross-Sectional Studies , Ethnicity , Female , Genotype , Humans , Hypertension/ethnology , Hypertension/physiopathology , Kidney Diseases/ethnology , Kidney Diseases/physiopathology , Male , Middle Aged , Outcome Assessment, Health Care , Risk Factors , United States/epidemiology
18.
Hypertension ; 75(5): 1167-1178, 2020 05.
Article in English | MEDLINE | ID: mdl-32172619

ABSTRACT

Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.


Subject(s)
Hypertension/epidemiology , Obesity/epidemiology , Adult , Africa/epidemiology , Aged , Antihypertensive Agents/therapeutic use , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Overweight/epidemiology , Prevalence , Risk Factors
19.
Liver Int ; 40(4): 889-893, 2020 04.
Article in English | MEDLINE | ID: mdl-31965669

ABSTRACT

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic/Latinos and rates of NAFLD vary among Hispanics from different background groups. Genetic variants and continental ancestry contribute to NAFLD disparities among Hispanics. We evaluated two newly identified NAFLD-associated single nucleotide polymorphisms of HSD17B13, rs72613567:TA and rs62305723:A in Hispanics/Latinos. METHODS: Clinical data, genotypes of variants of interest and estimates of continental ancestry were extracted from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) database, which includes a cohort of 16 415 US Hispanic/Latinos. Surrogate endpoints for NAFLD were suspected NAFLD based on unexplained aminotransferase elevation, continuous ALT levels and FIB-4 scores to estimate hepatic fibrosis. RESULTS: In all, 9342 participants were included for analysis. The rs72613567:TA allele was found in 15.3% and the rs62305723:A allele was identified in 4.5% of HCHS/SOL participants. rs72613567:TA was less frequent in persons with vs without suspected NAFLD (12.4% vs 15.7%, P < .001) and rs72613567:TA was associated with lower FIB-4 scores (P = .01). For persons with the NAFLD-associated PNPLA3 rs738409:G allele, the presence of rs72613567:TA was associated with a lower rate of suspected NAFD (odds ratio = 0.76, P < .001). rs72613567:TA was less frequent in Hispanic/Latino background groups with higher rates of suspected NAFLD. The rs62305723:A allele was not associated with suspected NAFLD or FIB-4 score. CONCLUSION: The rs72613567:TA allele is associated with lower rates of suspected NAFLD and lower FIB-4 scores among Hispanic/Latinos and with lower rates of suspected NAFLD in persons with the PNPLA3 rs738409:G allele. The rs72613567:TA allele contributes to NAFLD disparities among Hispanic/Latino background groups.


Subject(s)
17-Hydroxysteroid Dehydrogenases/genetics , Non-alcoholic Fatty Liver Disease , Hispanic or Latino/genetics , Humans , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease/ethnology , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single Nucleotide , Transaminases
20.
JMIR Res Protoc ; 9(1): e14820, 2020 Jan 17.
Article in English | MEDLINE | ID: mdl-31951214

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. OBJECTIVE: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. METHODS: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. RESULTS: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. CONCLUSIONS: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14820.

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