Browsing by Author "Jean-Tristan Brandenburg"

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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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    Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans
    (2022-02-14) Palwende Romuald Boua; Jean-Tristan Brandenburg; Ananyo Choudhury; Hermann Sorgho; Engelbert A Nonterah; Godfred Agongo; Gershim Asiki; Lisa Micklesfield; Solomon Choma; Francesc Xavier Gómez-Olivé; Scott Hazelhurst; Halidou Tinto; Nigel J Crowther; Christopher G Mathew; Michèle Ramsay
    Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies.
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    Genetic Susceptibility to Breast Cancer in SubSaharan African Populations
    Mahtaab Hayat; Wenlong Chen; Jean-Tristan Brandenburg; Chantal Babb; Michele Ramsay; Christopher Mathew
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    Genome-wide association study of population-standardised cognitive performance phenotypes in a rural South African community.
    (2023-03-27) Cassandra C. Soo; Jean-Tristan Brandenburg; Almut Nebel; Stephen Tollman; Lisa Berkman; Michèle Ramsay; Ananyo Choudhury
    Cognitive function is an indicator for global physical and mental health, and cognitive impairment has been associated with poorer life outcomes and earlier mortality. A standard cognition test, adapted to a rural-dwelling African community, and the Oxford Cognition Screen-Plus were used to capture cognitive performance as five continuous traits (total cognition score, verbal episodic memory, executive function, language, and visuospatial ability) for 2,246 adults in this population of South Africans. A novel common variant, rs73485231, reached genome-wide significance for association with episodic memory using data for ~14 million markers imputed from the H3Africa genotyping array data. Windowbased replication of previously implicated variants and regions of interest support the discovery of African-specific associated variants despite the small population size and low allele frequency. This African genome-wide association study identifies suggestive associations with general cognition and domain-specific cognitive pathways and lays the groundwork for further genomic studies on cognition in Africa.
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    Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits
    (2022-05-11) Ananyo Choudhury; Jean-Tristan Brandenburg; Tinashe Chikowore; Dhriti Sengupta; Palwende Romuald Boua; Nigel J. Crowther; Godfred Agongo; Gershim Asik; F. Xavier Gómez-Olivé; Isaac Kisiangani; Eric Maimela; Matshane Masemola-Maphutha; Lisa K. Micklesfield; Engelbert A. Nonterah; Shane A. Norris; Hermann Sorgho; Halidou Tinto; Stephen Tollman; Sarah E. Graham; Cristen J. Willer; AWI-Gen study; H3Africa Consortium; Scott Hazelhurst; Michèle Ramsay
    Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10−8). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10−8). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data.
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    Prevalence and Reclassification of Genetic Variants in South African Populations with Breast Cancer
    Tabitha Osler; Jean-Tristan Brandenburg; M Schoeman; Wenlong Chen; Michael Urban; Christopher Mathew
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    Systematic Review of Genomic Associations with Blood Pressure and Hypertension in Populations with AfricanAncestry
    Surina Singh; Jean-Tristan Brandenburg; Ananyo Choudhury; Francesc Gomez-Olive Casas; Michele Ramsay