Browsing by Author "Scott Hazelhurst"
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Item A systematic comparison of pharmacogene star allele calling bioinformatics algorithms a focus on CYP2D6 genotypingDavid Twesigomwe; Galen EB Wright; Britt Drogemoller; Jorge Da Rocha; Zane Lombard; Scott HazelhurstItem Assessing the human health risks of indoor PM25 exposure in urban and rural households in two provinces of South Africa(PERGAMON-ELSEVIER SCIENCE LTD) Ngwako Kwatala; Siyathemba Kunene; Lisa Micklesfield; Sizwe Bongathini Zondo; Scott Hazelhurst; Francesc Gomez-Olive Casas; C Wright; Matthew Benyon; Roseanne D. Diab; N Naidoo; et alItem Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in SubSaharan African PopulationsDavid Twesigomwe; Britt I. Drogemoller; Galen E.B Wright; Clement Adebamowo; Godfred Agongo; Palwende Boua; Mogomotsi Matshaba; Maria Paximadis; Michele Ramsay; Gustave Simo; Martin C. Simuunza; Caroline Tiemessen; Zane Lombard; Scott HazelhurstItem Characterization of CYP2C19 pharmacogenetic variation in African populations and comparison with other global populationsRoss Booyse; David Twesigomwe; Scott HazelhurstItem Expanding the human gut microbiome atlas of Africa(NATURE PUBLISHING GROUP) Dylan Maghini; Ovokeraye Oduaran; Luicer Olubayo; Jane A. Cook; Natalie Smyth; Theophilous Mathema; Grace-Anne Belger; G Agongo; Palwende Boua; Solomon Choma; Francesc Gomez-Olive Casas; I Kisiangani; R Mashaba; Lisa Micklesfield; Shane Norris; Stephen Tollman; Floidy Wafawanaka; Furahini Tluway; Michele Ramsay; Scott Hazelhurst; et alItem Genetic Association and Transferability for Urinary AlbuminCreatinine Ratio as a Marker of Kidney Disease in four SubSaharan African Populations and noncontinental Individuals of African AncestryJean-Tristan Brandenburg; Wenlong Chen; Palwende Boua; Melanie A Govender; G Agongo; Lisa Micklesfield; H Sorgho; Stephen Tollman; G Asiki; Scott Hazelhurst; June Fabian; Michele Ramsay; E et alItem 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 RamsayAtherosclerosis 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.Item Genomic and environmental risk factors for cardiometabolic diseases in Africa: methods used for Phase 1 of the AWI-Gen population cross-sectional study(2018-07-12) Stuart A. Al; Cassandra Soo; Godfred Agongo; Marianne Alberts; Lucas Amenga-Etego; Romuald P. Boua; Ananyo Choudhury; Nigel J. Crowther; Cornelius Depuur; F. Xavier GómezOlivé; Issa Guiraud; Tilahun N. Haregu; Scott Hazelhurst; Kathleen Kahn; Christopher Khayeka-Wandabwa; Catherine Kyobutung; Zané Lombard; Felistas Mashinya; Lisa Micklesfield; Shukri F. Mohamed; Freedom Mukomana; Seydou Nakanabo-Diallo; Hamtandi M. Natama; Nicholas Ngomi; Engelbert A. Nonterah; Shane A. Norris; Abraham R. Oduro; Athanase M. Somé; Hermann Sorgho; Paulina Tindana; Halidou Tinto; Stephen Tollman; Rhian Twine; Alisha Wade; Osman Sankoh; Michèle RamsayThere is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continentItem Household PM25 in a South African urban and rural setting A comparative analysis using lowcost sensors(TURKISH NATL COMMITTEE AIR POLLUTION RES & CONTROL-TUNCAP) M Benyon; Ngwako Kwatala; Tracy Laban; T Kapwata; C Batini; Samuel Cai; Lisa Micklesfield; Siyathemba Kunene; Sizwe Zondo; Scott Hazelhurst; Francesc Gomez-Olive Casas; et alItem Impact of pneumococcal conjugate vaccines on invasivepneumococcal diseasecausing lineages among South African children(NATURE PUBLISHING GROUP) Cebili Lekhuleni; K Ndlangisa; Rebecca A Gladstone; S Chochua; Benjamin J Metcalf; et.al et.al; Jacoba Kleynhans; Scott Hazelhurst; Sibongile Walaza; Cheryl Cohen; Anne Von Gottberg; Mignonette Du PlessisItem 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 RamsayGenetic 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.Item Short- and long-read metagenomics of urban and rural South African gut microbiomes reveal a transitional composition and undescribed taxa(2022-02-22) Fiona B Tamburini; Dylan Maghini; Ovokeraye H Oduaran; Ryan Brewster; Michaella R Hulley; Venesa Sahibdeen; Shane A Norris; Stephen Tollman; Kathleen Kahn; Ryan G Wagner; Alisha N Wade; Floidy Wafawanaka; F Xavier Gómez-Olivé; Rhian Twine; Zané Lombard; H3Africa AWI-Gen Collaborative Centre; Scott Hazelhurst; Ami S BhattHuman gut microbiome research focuses on populations living in high-income countries and to a lesser extent, non-urban agriculturalist and hunter-gatherer societies. The scarcity of research between these extremes limits our understanding of how the gut microbiota relates to health and disease in the majority of the world's population. Here, we evaluate gut microbiome composition in transitioning South African populations using short- and long-read sequencing. We analyze stool from adult females living in rural Bushbuckridge (n = 118) or urban Soweto (n = 51) and find that these microbiomes are taxonomically intermediate between those of individuals living in high-income countries and traditional communities. We demonstrate that reference collections are incomplete for characterizing microbiomes of individuals living outside high-income countries, yielding artificially low beta diversity measurements, and generate complete genomes of undescribed taxa, including Treponema, Lentisphaerae, and Succinatimonas. Our results suggest that the gut microbiome of South Africans does not conform to a simple "western-nonwestern" axis and contains undescribed microbial diversity.