Browsing by Author "Boua, Palwende Romuald"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    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.
  • No Thumbnail Available
    Item
    Genome-wide association study of carotid intima-media thickness (cIMT) in sub-Saharan African populations: An AWI-Gen study
    (2020) Boua, Palwende Romuald
    It is estimated that by 2020 cardiovascular diseases (CVDs) will be the leading cause of death. The demographic and health transition in sub-Saharan Africa (SSA) has shifted the major causes of mortality from communicable and nutritional diseases to non-communicable diseases (NCDs). Atherosclerosis is a complex, progressive disorder affecting large and medium-sized arteries, preceding the development of CVDs such as ischemic heart disease, stroke, heart failure, peripheral arterial disease and rheumatic heart disease. Despite the epidemiological complexity of CVDs in SSA, the genetic susceptibility of the populations has remained understudied. Genome-wide association studies (GWAS) have revolutionized the field of complex disease genetics over the past decade, and provided insights into the genetic architecture of disease susceptibility and to advances in clinical care and personalized medicine. The evolutionary roots and genetic diversity of the continent represent an opportunity to shed new light on the genetic architecture of complex traits such as atherosclerosis. This thesis used the AWI-Gen (Africa Wits-INDEPTH Partnership for Genomic Studies) data to investigate whether genetic variation in SSA populations is associated with carotid intimamedia thickness (cIMT) (a marker for atherosclerosis) in middle-aged adults (40-60 years of age) and to examine interactions with key environmental factors. First, cIMT distributions in four SSA countries were characterised (Chapter 2). West African populations had higher cIMT compared to East and South Africa, despite having a lower prevalence of CVDs risk factors. West Africans also had higher cIMT compared to Asians and Europeans, but were concordant with data in African Americans, a trend not observed for East and South Africans. Our study is the first to report age-specific reference intervals of cIMT in SSA from a population-based study. Second, genetic susceptibility to atherosclerosis in SSA was investigated by performing a GWAS on 7894 unrelated middle-aged adults (3963 women, 3931 men) from the AWI-Gen study (with participants from East, South and West Africa), with adjustment for age, sex and 8 principal components (PCs) (Chapter 3). cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array (~2.3M SNPs). After imputation, we tested for association using BOLT-LMM. We identified two new African-specific genome-wide significant cIMT-associated loci (SIRPA (p=4.7E-08) and FBXL17 (p=2.5E-08)). Sex-stratification analysis revealed two male-specific loci (SNX29 (p=6.3E-9) and MAP3K7 (p=5.3E-8)), and two female-specific loci (ARNT2 (p=2.4E-09) and PROK1 (p=1.0E-08)). We also successfully replicated known cIMT-associated loci and identified novel African-specific variant and gene associations. Finally, we investigated gene-smoking interaction on cIMT in men from West Africa (Chapter 4). In Nanoro we identified new variants for the gene-smoking interactions for cIMT within the previously described RCBTB1 region (p-value=3.08E-08), and identified a new region at BCHE (p=2.20E-08). In the combined sample, variants were identified in the regulatory region and in a region of open chromatin of TBC1D8 (p-value=5.90E-09). Our study highlighted sex differences in atherosclerosis risk, and the role of gene-environment interaction. There was transferability of signals from studies of non-African populations, providing opportunities for fine-mapping and reducing credible SNP sets using African data. Greater inclusion of African populations in medical genomics is important for accelerating discoveries and identifying new genetic associations with traits for variants absent from other populations. Gene-environment interaction studies provide an opportunity for prevention and a precision public health approach.