Browsing by Author "Agongo, Godfred"

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    Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations
    (2022-06) Jean-Tristan Brandenburg; Melanie A. Govender; Winkler, Cheryl A.; Boua, Palwende Romuald; Agongo, Godfred; Fabian, June; Ramsay, Michèle
    Background and objectives: Recessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa. Design, setting, participants, & measurements: This cross-sectional population-based study in four African countries included 10,769 participants largely aged 40-60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria. Results: High G1 allele frequencies occurred in South and West Africa (approximately 7%-13%). G2 allele frequencies were highest in South Africa (15%-24%), followed by West Africa (9%-12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed. Conclusions: APOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.
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    The effect of genetic variants, anthropometry and the environment on lipid profile in adults in Northern Ghana
    (2019) Agongo, Godfred
    Genetic polymorphisms, environmental factors and gene-environment interactions are associated with variations in lipid levels. This evidence comes from studies in mainly Europeans and people of African descent but little or no data exists on the influence of these factors on lipid levels in indigenous black African populations. The aim of the current study was therefore to characterize the principal environmental and genetic factors that influence serum lipid levels in a rural, adult Ghanaian population and to determine if gene-environment interactions further modulate lipid levels. It was a cross-sectional survey that recruited 2016 men and women resident in the study area and aged 40-60 years. Self-reported socio-demographic and behavioural data were collected using a structured questionnaire. Simple anthropometric measures were taken using standardised procedures and visceral and abdominal subcutaneous adipose tissue thickness were measured using ultrasound. Whole blood was collected for DNA extraction and serum was used for the measurement of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG). Genotyping of candidate genes was performed using the H3Africa single nucleotide variant genotyping array. Multivariable linear regression analysis was used to test the association of environmental factors with lipid levels. The effect of genetic polymorphisms and geneenvironment interaction on lipid levels was tested using regression models with Bonferroniadjusted p values. The prevalence of dyslipidaemia among the total population was as follows: low HDL-C: 60.30%, high LDL-C=5.55%, high TC=4.02% and high TG=2.12%. A greater proportion of women had low HDL-C compared to men (p=0.005). Subcutaneous abdominal fat was associated with TC (β=0.067, p=0.015) and TG (β=0.137, p<0.001) among women and LDL-C (β=0.139, p=0.006) and TC (β=0.071, p=0.048) among men. Body mass index was associated with TC (β=0.010, p=0.043) among men while waist circumference was associated with LDL-C (β=0.116, p<0.001) and TG (β=0.094, p<0.001) among women. Hip circumference was negatively associated (β=-0.053, p=0.043), while visceral fat was positively associated with TG (β=0.033, p=0.022) among women. Socioeconomic status, education, being unmarried and employment were associated with HDL-C (β=0.081, p=0.004), LDL-C (β=0.095, p=0.004) and TG (β=0.095, p=0.001) respectively, all among women, and TC (β=0.070, p=0.010) among men. Tobacco smoking (β=0.066, p=0.024) among men and alcohol intake among women (β=0.084, p=0.001) were associated with HDL-C levels. For the genetic association analysis the lead variants for association with HDL-C were rs17231520 (β=0.139, p<0.0001) and rs34065661 (β=0.137, p<0.0001), both in CETP. The interaction between tobacco smoking and ABCA1 (rs10124686) was associated with higher TC levels (p=0.041) while that between CETP (rs34620476) and tobacco smoking was associated with lower TG levels in men (p=0.020). Associations of education, employment and adiposity with lipid levels suggest that future societal advances and increases in the prevalence of obesity may lead to associated adverse health consequences. Variants in CETP strongly modulate HDL-C levels in the study population. Total cholesterol and TG levels may be modestly influenced by gene-environment interactions of ABCA1 and CETP, respectively, with smoking among men in the study population.
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    Genomewide association study metaanalysis of blood pressure traits and hypertension in subSaharan African populations an AWIGen study
    (Nature Research) Norris, Shane A.; Choudhury, Ananyo; Hazelhurst, Scott ; Crowther, Nigel ; Boua, Palwende ; Sorgho, Hermann; Agongo, Godfred; Nonterah, Engelbert A.; Micklesfield, Lisa K.; Singh, Surina; Kisiangani, Isaac; Mohamed, Shukri; Gomez-Olive, Francesc X.; Tollman, Stephen M.; Choma, Solomon; Brandenburg, J-T.; Ramsay, Michele