Publications

@article{Brandenburg2024,

title = {Genetic Association and Transferability for Urinary Albumin-Creatinine Ratio as a Marker of Kidney Disease in four Sub-Saharan African Populations and non-continental Individuals of African Ancestry},

author = {Jean-Tristan Brandenburg and Wenlong Carl Chen and Palwende Romuald Boua and Melanie Ann Govender and Godfred Agongo and Lisa K Micklesfield and Hermann Sorgho and Stephen Tollman and Gershim Asiki and Felistas Mashinya and Scott Hazelhurst and Andrew P Morris and June Fabian and Mich\`{e}le Ramsay},

url = {https://pubmed.ncbi.nlm.nih.gov/38293229/ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC10827237},

doi = {10.1101/2024.01.17.24301398},

year  = {2024},

date = {2024-01-01},

journal = {medRxiv : the preprint server for health sciences},

publisher = {medRxiv},

abstract = {BACKGROUND Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts. METHODS Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. RESULTS Two genome-wide significant (P\<5x10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. CONCLUSION This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes. METHODS Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations. RESULTS Two genome-wide significant (P\<5x10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained. CONCLUSION This study contributes novel insights into the genetic architecture of kidney function in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations.},

keywords = {doi:10.1101/2024.01.17.24301398, Jean-Tristan Brandenburg, MEDLINE, Mich\`{e}le Ramsay, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, PMC10827237, pmid:38293229, Preprint, PubMed Abstract, Wenlong Carl Chen},

pubstate = {published},

tppubtype = {article}

}

@article{Hazelhurst2024,

title = {Computation of Socio-Economic Status in the AWI-Gen Project},

author = {Scott Hazelhurst and Palwend\'{e} Boua and Ananyo Choudhury and Siyanda Madala and Dhriti Sengupta and Furahini Tluway and Mich\`{e}le Ramsay},

url = {https://pubmed.ncbi.nlm.nih.gov/39228720/ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC11370514},

doi = {10.1101/2024.08.22.24312411},

year  = {2024},

date = {2024-01-01},

journal = {medRxiv : the preprint server for health sciences},

publisher = {medRxiv},

abstract = {Socio-economic status of participants in many public health, epidemiological, and genome-wide association studies is an important trait of interest. It is often used in these studies as a measure of direct interest or as a covariate. The Africa Wits INDEPTH Partnership for Genomic and Environmental Research (AWI-Gen) explores genomic and environmental factors in non-communicable diseases, particularly cardio-metabolic disease. In Phase I of AWI-Gen, approximately 12,000 participants were recruited at six sites in four African countries. Participants were asked questions about asset ownership. This technical note describes how AWI-Gen computed socio-economic status from the asset register.},

keywords = {doi:10.1101/2024.08.22.24312411, MEDLINE, Mich\`{e}le Ramsay, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Palwend\'{e} Boua, PMC11370514, pmid:39228720, Preprint, PubMed Abstract, Scott Hazelhurst},

pubstate = {published},

tppubtype = {article}

}

@article{Singh2023,

title = {Genome-wide Association Study Meta-analysis of Blood Pressure Traits and Hypertension in Sub-Saharan African Populations: An AWI-Gen Study},

author = {Surina Singh and Ananyo Choudhury and Scott Hazelhurst and Nigel Crowther and Palwende Boua and Hermann Sorgho and Godfred Agongo and Engelbert Nonterah and Lisa Micklesfield and Shane Norris and Isaac Kisiangani and Shukri Mohamed and Francesc Gomez-Olive and Stephen Tollman and Solomon Choma and Jean-Tristan Brandenburg and Michele Ramsay},

url = {https://pubmed.ncbi.nlm.nih.gov/36824767/ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9949264},

doi = {10.21203/RS.3.RS-2532794/V1},

issn = {2693-5015},

year  = {2023},

date = {2023-01-01},

journal = {Research square},

publisher = {Res Sq},

abstract = {Most hypertension-related genome-wide association studies (GWAS) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure-related traits (systolic and diastolic blood pressure, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N=10,775), identified two genome-wide significant signals (p\<5E-08): systolic blood pressure near P2RY1 (rs77846204; intergenic variant},

keywords = {Ananyo Choudhury, doi:10.21203/rs.3.rs-2532794/v1, MEDLINE, Mich\`{e}le Ramsay, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, PMC9949264, pmid:36824767, Preprint, PubMed Abstract, Surina Singh},

pubstate = {published},

tppubtype = {article}

}