Browsing by Author "Palwende Romuald Boua"

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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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    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.