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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.

ABSTRACT: 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.

SUBMITTER: Singh S

PROVIDER: S-EPMC10725455 | biostudies-literature | 2023 Dec

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 J NJ Boua Palwendé R PR Sorgho Hermann H Agongo Godfred G Nonterah Engelbert A EA Micklesfield Lisa K LK Norris Shane A SA Kisiangani Isaac I Mohamed Shukri S Gómez-Olivé Francesc X FX Tollman Stephen M SM Choma Solomon S Brandenburg J-T JT Ramsay Michèle M

Nature communications 20231216 1

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): systo ...[more]

PMID: 38104120

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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.

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.

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.

Project description:BackgroundTo 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.MethodsAnthropometric 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.ResultsThe 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.ConclusionsAll 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.

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.

Dataset Information

Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study.

Publications

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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