Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits
Year: 2022
Type: review
Abstract: 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 theGATBregion (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 theGATB/FHIP1Aregion and identifies a novel triglyceride association signal close to theFHITgene (P-value =2.66 × 10−8). Our data enable fine-mapping of several well-known lipid-trait loci includingLDLR, PMFBP1andLPA. 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.
Source: Nature Communications
Authors: Ananyo Choudhury, Jean-Tristan Brandenburg, Tinashe Chikowore, Dhriti Sengupta, Palwende Romuald Boua, Nigel J. Crowther, Godfred Agongo, Gershim Asiki, 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, Scott Hazelhurst, Michèle Ramsay
Institutions: University of the Witwatersrand, South African Medical Research Council, Institut de Recherche en Sciences de la Santé, Clinical Research Unit Nanoro, National Health Laboratory Service, Navrongo Health Research Centre, Ghana Health Service, University of Technology and Applied Sciences, African Population and Health Research Center, Agincourt Health and Socio-Demographic Surveillance System, University of Limpopo, University of Michigan, Michigan Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Health and Human Services, Wellcome Trust, Department of Science and Technology, Ministry of Science and Technology, India, National Health Laboratory Service, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, Office of AIDS Research
Awards: Characterisation of gene-lifestyle interactions associated with obesity-related traits in African populations, G2350237985, G4878468429, G5416918554, Characterisation of gene-lifestyle interactions associated with obesity- related traits in African populations, G8357962960, G8466233299, AWI-Gen Phase 2: Genomic and environmental risk factors for cardiometabolic disease in Africans, Using genetics to discover mechanisms of abdominal aortic aneurysm
OpenAlex ID: W4280549199