Genome-wide Association Study Meta-analysis of Blood Pressure Traits and Hypertension in Sub-Saharan African Populations: An AWI-Gen Study.
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SUBMITTER: Singh S
PROVIDER: S-EPMC9949264 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Genome-wide Association Study Meta-analysis of Blood Pressure Traits and Hypertension in Sub-Saharan African Populations: An AWI-Gen Study.
Singh Surina S Choudhury Ananyo A Hazelhurst Scott S Crowther Nigel N Boua Palwende P Sorgho Hermann H Agongo Godfred G Nonterah Engelbert E Micklesfield Lisa L Norris Shane S Kisiangani Isaac I Mohamed Shukri S Gomez-Olive Francesc F Tollman Stephen S Choma Solomon S Brandenburg Jean-Tristan JT Ramsay Michele M
Research square 20230213
Most hypertension-related genome-wide association studies (GWAS) 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-related traits (systolic and diastolic blood pressure, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N=10,775), identified two genome-wide significant signals (p<5E-08): systolic ...[more]
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Project description: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.
| S-EPMC10725455 | biostudies-literature
Project description:The analysis of the effects of autozygosity, measured as the change of the mean value of a trait among offspring of genetic relatives, reveals the existence of directional dominance or overdominance. In this study we detect evidence of the effect of autozygosity in 4 out of 13 cardiometabolic disease-associated traits using data from more than 10,000 sub-Saharan African individuals recruited from Ghana, Burkina Faso, Kenya and South Africa. The effect of autozygosity on these phenotypes is found to be sex-related, with inbreeding having a significant decreasing effect in men but a significant increasing effect in women for several traits (body mass index, subcutaneous adipose tissue, low-density lipoproteins and total cholesterol levels). Overall, the effect of inbreeding depression is more intense in men. Differential effects of inbreeding depression are also observed between study sites with different night-light intensity used as proxy for urban development. These results suggest a directional dominant genetic component mediated by environmental interactions and sex-specific differences in genetic architecture for these traits in the Africa Wits-INDEPTH partnership for Genomic Studies (AWI-Gen) cohort.
| S-EPMC7666169 | biostudies-literature
Project description:BackgroundThe cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life's simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT).MethodsWe conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status.ResultsThe mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 μm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (β-coefficients [95% confidence interval]: Burkina Faso, - 6.51 [- 9.83, - 3.20] μm; Ghana, - 5.42 [- 8.90, - 1.95]; Kenya, - 6.58 [- 9.05, - 4.10]; and South Africa, - 7.85 [- 9.65, - 6.05]). Inverse relations were observed for women (- 4.44 [- 6.23, - 2.65]) and men (- 6.27 [- 7.91, - 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001).ConclusionThis large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.
| S-EPMC7874493 | biostudies-literature
Project description:BackgroundAfrican populations are characterised by diversity at many levels including: demographic history, genetic ancestry, language, wealth, socio-political landscape, culture and behaviour. Several of these have a profound impact on body fat mass. Obesity, a key risk factor for cardiovascular and metabolic diseases, in the wake of the epidemiological and health transitions across the continent, requires detailed analysis together with other major risk factors.ObjectiveTo compare regional and sex-specific body mass index (BMI) distributions, using a cross-sectional study design, in adults aged 40-60 years across six study sites in four sub-Saharan African (SSA) countries and to compare the determinants of BMI at each.MethodsAnthropometric measurements were standardised across sites and BMI calculated. Median BMI and prevalence of underweight, lean, overweight and obesity were compared between the sexes and across sites. Data from multivariable linear regression models for the principal determinants of BMI were summarised from the site-specific studies.ResultsBMI was calculated in 10,702 participants (55% female) and was significantly higher in women than men at nearly all sites. The highest prevalence of obesity was observed at the three South African sites (42.3-66.6% in women and 2.81-17.5% in men) and the lowest in West Africa (1.25-4.22% in women and 1.19-2.20% in men). Across sites, higher socio-economic status and educational level were associated with higher BMI. Being married and increased dietary intake were associated with higher BMI in some communities, whilst smoking and alcohol intake were associated with lower BMI, as was HIV infection in the regions where it was prevalent.ConclusionIn SSA there is a marked variation in the prevalence of obesity both regionally and between men and women. Our data suggest that the drive for social upliftment within Africa will be associated with rising levels of obesity, which will require the initiation of targeted sex-specific intervention programmes across specific African communities.
| S-EPMC6407581 | biostudies-literature
Project description:BackgroundObesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub-Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease.ObjectivesWe determined the association between various adiposity phenotypes and carotid intima-media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population.MethodsA population-based cross-sectional study was performed from 2013-2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta-analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses.ResultsData were obtained from 9,010 adults (50.3% women and a mean age of 50± 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI (β-value [95% CIs]: 19.5 [16.8, 22.3] μm) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] μm), SCAT (5.00 [2.85, 7.15] μm), WC (1.27 [1.09, 1.44] μm) and HC (1.23 [1.04, 1.42] μm). Stronger associations were observed in men than in women.ConclusionObesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation.HighlightsAll adiposity phenotypes were positively associated with common carotid intima-media thickness (CIMT) in the entire cohort (pooled analyses).BMI had the strongest association with CIMT compared to other phenotypes.The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women.Subcutaneous adipose tissue was inversely associated with CIMT only in women.An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana.
| S-EPMC7977036 | biostudies-literature
Project description:BACKGROUND:To report associations between different adiposity indices [anthropometric and dual-energy X-ray absorptiometry (DXA) measures] and blood pressure (BP) and hypertension in urban black South African adults. METHODS:Anthropometric and DXA whole body measures were performed on 1026 men and 982 women. Participants were classified as being hypertensive if they had a systolic BP (SBP)???140 mmHg and/or diastolic (DBP)???90 mmHg. Within each gender the relationship of adiposity with BP and hypertension risk was assessed using linear and logistic regression models respectively. Bivariate models were computed for each body composition variable. Furthermore, we computed a multiple regression model to illustrates how body composition parameters are associated with the outcome variables independent of each other. RESULTS:The males were significantly taller and had a higher fat free soft tissue mass (FFSTM), DBP and socio-economic status, and were more likely to use tobacco and be hypertensive (48.0% vs. 38.8%). The females had higher body mass index (BMI), waist circumference (WC), fat mass (FM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), FM/FFSTM ratio and body fat % than males. All body composition parameters were positively associated with hypertension. In both males and females, the FM/FFSTM ratio associated the strongest with hypertension illustrating the following odds ratios [males: 70.37 (18.47, 268.16) p ??0.001; females 2.48 (0.86,7.21) p =?0.09]. The multiple regression model, indicated that the VAT and WC significantly associated with both SBP and DBP in the men and women respectively, whilst WC was the only significant predictor for hypertension. CONCLUSIONS:All body composition parameters were associated with hypertension and FM/FFSTM ratio showed the strongest relationship. It was reassuring that WC remains a useful measure of central adiposity that can be used as a risk indicator for hypertension if more sophisticated measures are not available. Furthermore, our data in part, implies that reducing abdominal adiposity in aging adults could contribute to reducing the risk of elevated blood pressure and hypertension.
| S-EPMC5907712 | biostudies-literature
Project description:IntroductionAtherosclerosis is a key contributor to the burden of cardiovascular diseases (CVDs) and many epidemiological studies have reported on the effect of smoking on carotid intima-media thickness (cIMT) and its subsequent effect on CVD risk. Gene-environment interaction studies have contributed towards understanding some of the missing heritability of genome-wide association studies. Gene-smoking interactions on cIMT have been studied in non-African populations (European, Latino-American, and African American) but no comparable African research has been reported. Our aim was to investigate smoking-SNP interactions on cIMT in two West African populations by genome-wide analysis.Materials and methodsOnly male participants from Burkina Faso (Nanoro = 993) and Ghana (Navrongo = 783) were included, as smoking was extremely rare among women. Phenotype and genotype data underwent stringent QC and genotype imputation was performed using the Sanger African Imputation Panel. Smoking prevalence among men was 13.3% in Nanoro and 42.5% in Navrongo. We analyzed gene-smoking interactions with PLINK after adjusting for covariates: age and 6 PCs (Model 1); age, BMI, blood pressure, fasting glucose, cholesterol levels, MVPA, and 6 PCs (Model 2). All analyses were performed at site level and for the combined data set.ResultsIn Nanoro, we identified new gene-smoking interaction variants for cIMT within the previously described RCBTB1 region (rs112017404, rs144170770, and rs4941649) (Model 1: p = 1.35E-07; Model 2: p = 3.08E-08). In the combined sample, two novel intergenic interacting variants were identified, rs1192824 in the regulatory region of TBC1D8 (p = 5.90E-09) and rs77461169 (p = 4.48E-06) located in an upstream region of open chromatin. In silico functional analysis suggests the involvement of genes implicated in biological processes related to cell or biological adhesion and regulatory processes in gene-smoking interactions with cIMT (as evidenced by chromatin interactions and eQTLs).DiscussionThis is the first gene-smoking interaction study for cIMT, as a risk factor for atherosclerosis, in sub-Saharan African populations. In addition to replicating previously known signals for RCBTB1, we identified two novel genomic regions (TBC1D8, near BCHE) involved in this gene-environment interaction.
| S-EPMC7025492 | biostudies-literature
Project description:BackgroundThere is growing support for the use of genetic risk scores (GRS) in routine clinical settings. Due to the limited diversity of current genomic discovery samples, there are concerns that the predictive power of GRS will be limited in non-European ancestry populations. GRS for cardiometabolic traits were evaluated in sub-Saharan Africans in comparison with African Americans and European Americans.MethodsWe evaluated the predictive utility of GRS for 12 cardiometabolic traits in sub-Saharan Africans (AF; n = 5200), African Americans (AA; n = 9139) and European Americans (EUR; n = 9594). GRS were constructed as weighted sums of the number of risk alleles. Predictive utility was assessed using the additional phenotypic variance explained and the increase in discriminatory ability over traditional risk factors [age, sex and body mass index (BMI)], with adjustment for ancestry-derived principal components.ResultsAcross all traits, GRS showed up to a 5-fold and 20-fold greater predictive utility in EUR relative to AA and AF, respectively. Predictive utility was most consistent for lipid traits, with percentage increase in explained variation attributable to GRS ranging from 10.6% to 127.1% among EUR, 26.6% to 65.8% among AA and 2.4% to 37.5% among AF. These differences were recapitulated in the discriminatory power, whereby the predictive utility of GRS was 4-fold greater in EUR relative to AA and up to 44-fold greater in EUR relative to AF. Obesity and blood pressure traits showed a similar pattern of greater predictive utility among EUR.ConclusionsThis work demonstrates the poorer performance of GRS in AF and highlights the need to improve representation of multiple ethnic populations in genomic studies to ensure equitable clinical translation of GRS.
| S-EPMC8407873 | biostudies-literature
Project description:BACKGROUND:Rapid epidemiological health transitions occurring in vulnerable populations in Africa that have an existing burden of infectious and non-communicable diseases predict an increased risk and consequent prevalence of kidney disease. However, few studies have characterised the true burden of kidney damage and associated risk factors in Africans. We investigated the prevalence of markers for kidney damage and known risk factors in rural and urban settings in sub-Saharan Africa. METHODS:In this cross-sectional population study (Africa Wits-International Network for the Demographic Evaluation of Populations and their Health Partnership for Genomic Studies [AWI-Gen]), we recruited unrelated adult participants aged 40-60 years from four rural community research sites (Nanoro, Burkina Faso; Navrongo, Ghana; Agincourt and Dikgale, South Africa), and two urban community research sites (Nairobi, Kenya; and Soweto, South Africa). Participants were identified and selected using random sampling frames already in use at each site. Participants completed a lifestyle and medical history questionnaire, had anthropometric and blood pressure measurements taken, and blood and urine samples were collected. Markers of kidney damage were defined as low estimated glomerular filtration rate (eGFR; <60 mL/min per 1·73 m2), presence of albuminuria (urine albumin creatinine ratio >3 mg/mmol); or chronic kidney disease (low eGFR or albuminuria, or both). We calculated age-adjusted prevalence of chronic kidney disease, low eGFR, and albuminuria by site and sex and used logistic regression models to assess risk factors of kidney damage. FINDINGS:Between August, 2013, and August, 2016, we recruited 10?702 participants, of whom 8110 were analysable. 4120 (50·8%) of analysable participants were male, with a mean age of 49·9 years (SD 5·8). Age-standardised population prevalence was 2·4% (95% CI 2·1-2·8) for low eGFR, 9·2% (8·4-10·0) for albuminuria, and 10·7% (9·9-11·7) for chronic kidney disease, with higher prevalences in South African sites than in west African sites (14·0% [11·9-16·4] in Agincourt vs 6·6% [5·5-7·9] in Nanoro). Women had a higher prevalence of chronic kidney disease (12·0% [10·8-13·2] vs 9·5% [8·3-10·8]) and low eGFR (3·0% [2·6-3·6] vs 1·7% [1·3-2·3]) than did men, with no sex-specific differences for albuminuria (9·9% [8·8-11·0] vs 8·4% [7·3-9·7]). Risk factors for kidney damage were older age (relative risk 1·04, 95% CI 1·03-1·05; p<0·0001), hypertension (1·97, 1·68-2·30; p<0·0001), diabetes (2·22, 1·76-2·78; p<0·0001), and HIV (1·65, 1·36-1·99; p<0·0001); whereas male sex was protective (0·85, 0·73-0·98; p=0·02). INTERPRETATION:Regional differences in prevalence and risks of chronic kidney disease in sub-Saharan Africa relate in part to varying stages of sociodemographic and epidemiological health transitions across the area. Public health policy should focus on integrated strategies for screening, prevention, and risk factor management in the broader non-communicable disease and infectious diseases framework. FUNDING:National Human Genome Research Institute, Office of the Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, the Office of AIDS Research, and National Institute of Diabetes and Digestive and Kidney Diseases, all of the National Institutes of Health, and the South African Department of Science and Technology.
| S-EPMC7033368 | biostudies-literature
Project description:Systolic (SBP) and diastolic blood pressure (DBP) are commonly used for cardiovascular disease (CVD) risk prediction, and pulse pressure (PP) and mean arterial blood pressure (MAP) can provide additional information. It is therefore important to understand the factors associated with these cardiovascular risk markers. This cross-sectional study involved 1839 men and women aged 40-60 years. Data on SBP, DBP, MAP, PP, sociodemography, lifestyle, anthropometry, and lipids were collected. Gender-stratified linear regression analyses were performed to determine the association between log-transformed blood pressure indices and the study variables. Age was associated with all measured blood pressure indices (p < 0.001) among men and women. Men had higher SBP (p=0.007) and PP (p < 0.001) than women. Nankana ethnicity was associated with higher PP levels (p < 0.005) in the total population. Vendor meal consumption among women was associated with higher PP levels (p < 0.05). Fruit intake among men was associated with lower PP levels (p < 0.05). Currently unmarried women had higher SBP (p < 0.005), DBP (p < 0.05), MAP (p < 0.005), and PP (p < 0.005) than currently married women. Pesticide exposure was negatively associated with SBP (p < 0.005), DBP (p < 0.005), MAP (p < 0.005), and PP (p < 0.05) among women. Increased subcutaneous fat was associated with DBP (p < 0.005) and MAP (p < 0.05) among women. Among men, hip circumference was associated with higher DBP and MAP (p < 0.05 for both associations), subcutaneous fat associated with higher SBP (p < 0.005), DBP (p < 0.001), and MAP (p < 0.001) and visceral fat was associated with higher PP (p < 0.05). In the total population, visceral fat was associated with higher DBP (p < 0.05) and MAP (p < 0.001). High-density lipoprotein cholesterol was positively associated with SBP (p < 0.005), DBP (p < 0.005), and MAP (p < 0.001) for women and positively associated with SBP, DBP, and MAP (p < 0.001 for all three) and PP (p < 0.05) for men. The association of blood pressure indices with modifiable risk factors suggests that targeted health interventions may reduce CVD risk in this population.
| S-EPMC7201512 | biostudies-literature