Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits

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, Scott Hazelhurst and Michèle Ramsay ()
Additional contact information
Ananyo Choudhury: University of the Witwatersrand
Jean-Tristan Brandenburg: University of the Witwatersrand
Tinashe Chikowore: University of the Witwatersrand
Dhriti Sengupta: University of the Witwatersrand
Palwende Romuald Boua: University of the Witwatersrand
Nigel J. Crowther: University of the Witwatersrand
Godfred Agongo: Ghana Health Service
Gershim Asiki: African Population and Health Research Center
F. Xavier Gómez-Olivé: University of the Witwatersrand
Isaac Kisiangani: African Population and Health Research Center
Eric Maimela: University of Limpopo
Matshane Masemola-Maphutha: University of Limpopo
Lisa K. Micklesfield: University of the Witwatersrand
Engelbert A. Nonterah: Ghana Health Service
Shane A. Norris: University of the Witwatersrand
Hermann Sorgho: Institut de Recherche en Sciences de la Santè
Halidou Tinto: Institut de Recherche en Sciences de la Santè
Stephen Tollman: University of the Witwatersrand
Sarah E. Graham: University of Michigan
Cristen J. Willer: University of Michigan
Scott Hazelhurst: University of the Witwatersrand
Michèle Ramsay: University of the Witwatersrand

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30098-w

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