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 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.

Genetic associations and polygenic scores for lipid traits have low transferability to African individuals. Here, the authors perform a large sub-Sarahan African lipid GWAS and find that larger datasets and better global representation in discovery GWAS help to bridge this gap.

Details

Title
Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits
Author
Choudhury, Ananyo 1   VIAFID ORCID Logo  ; Brandenburg, Jean-Tristan 1   VIAFID ORCID Logo  ; Chikowore, Tinashe 2 ; Sengupta, Dhriti 1 ; Boua, Palwende Romuald 3   VIAFID ORCID Logo  ; Crowther, Nigel J. 4 ; Agongo, Godfred 5 ; Asiki, Gershim 6   VIAFID ORCID Logo  ; Gómez-Olivé, F. Xavier 7   VIAFID ORCID Logo  ; Kisiangani, Isaac 6 ; Maimela, Eric 8 ; Masemola-Maphutha, Matshane 9 ; Micklesfield, Lisa K. 10   VIAFID ORCID Logo  ; Nonterah, Engelbert A. 11   VIAFID ORCID Logo  ; Norris, Shane A. 10   VIAFID ORCID Logo  ; Sorgho, Hermann 12 ; Tinto, Halidou 12 ; Tollman, Stephen 7   VIAFID ORCID Logo  ; Graham, Sarah E. 13   VIAFID ORCID Logo  ; Willer, Cristen J. 14   VIAFID ORCID Logo  ; Hazelhurst, Scott 15   VIAFID ORCID Logo  ; Ramsay, Michèle 16   VIAFID ORCID Logo 

1  University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
2  University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135); University of the Witwatersrand, South African Medical Research Council/University of the Witwatersrand Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
3  University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135); Institut de Recherche en Sciences de la Santè, Clinical Research Unit of Nanoro, Nanoro, Burkina Faso (GRID:grid.457337.1) (ISNI:0000 0004 0564 0509) 
4  University of the Witwatersrand, Department of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
5  Ghana Health Service, Navrongo Health Research Centre, Navrongo, Ghana (GRID:grid.434994.7) (ISNI:0000 0001 0582 2706); C.K. Tedam University of Technology and Applied Sciences, Navrongo, Ghana (GRID:grid.434994.7) 
6  African Population and Health Research Center, Nairobi, Kenya (GRID:grid.413355.5) (ISNI:0000 0001 2221 4219) 
7  University of the Witwatersrand, MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
8  University of Limpopo, Department of Public Health, School of Health Care Sciences, Faculty of Health Sciences, Polokwane, South Africa (GRID:grid.411732.2) (ISNI:0000 0001 2105 2799) 
9  University of Limpopo, Department of Pathology and Medical Sciences, School of Health Care Sciences, Faculty of Health Sciences, Polokwane, South Africa (GRID:grid.411732.2) (ISNI:0000 0001 2105 2799) 
10  University of the Witwatersrand, South African Medical Research Council/University of the Witwatersrand Developmental Pathways for Health Research Unit, Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
11  Ghana Health Service, Navrongo Health Research Centre, Navrongo, Ghana (GRID:grid.434994.7) (ISNI:0000 0001 0582 2706) 
12  Institut de Recherche en Sciences de la Santè, Clinical Research Unit of Nanoro, Nanoro, Burkina Faso (GRID:grid.457337.1) (ISNI:0000 0004 0564 0509) 
13  University of Michigan, Department of Internal Medicine, Division of Cardiology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
14  University of Michigan, Department of Internal Medicine, Division of Cardiology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Human Genetics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
15  University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135); University of the Witwatersrand, School of Electrical and Information Engineering, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
16  University of the Witwatersrand, Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135); University of the Witwatersrand, Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-30098-w
ProQuest document ID
2662180731
Copyright
© The Author(s) 2022. corrected publication 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.