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; AWI-Gen study; H3Africa Consortium; Scott Hazelhurst; Michèle Ramsay

doi:10.1038/s41467-022-30098-w

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

Nat Commun. 2022 May 11;13(1):2578. doi: 10.1038/s41467-022-30098-w.

Authors

Ananyo Choudhury^#¹, Jean-Tristan Brandenburg^#², Tinashe Chikowore^{2

3}, Dhriti Sengupta², Palwende Romuald Boua^{2

4}, Nigel J Crowther⁵, Godfred Agongo^{6

7}, Gershim Asiki⁸, F Xavier Gómez-Olivé⁹, Isaac Kisiangani⁸, Eric Maimela¹⁰, Matshane Masemola-Maphutha¹¹, Lisa K Micklesfield³, Engelbert A Nonterah⁶, Shane A Norris³, Hermann Sorgho⁴, Halidou Tinto⁴, Stephen Tollman⁹, Sarah E Graham¹², Cristen J Willer^{12

13

14}; AWI-Gen study; H3Africa Consortium; Scott Hazelhurst^{2

15}, Michèle Ramsay^{16

17}

Affiliations

¹ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Ananyo.Choudhury@wits.ac.za.
² Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ 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, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santè, Nanoro, Burkina Faso.
⁵ Department of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁶ Navrongo Health Research Centre, Ghana Health Service, Navrongo, Ghana.
⁷ C.K. Tedam University of Technology and Applied Sciences, Navrongo, Ghana.
⁸ African Population and Health Research Center, Nairobi, Kenya.
⁹ MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹⁰ Department of Public Health, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo, Polokwane, South Africa.
¹¹ Department of Pathology and Medical Sciences, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo, Polokwane, South Africa.
¹² Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, 48109, USA.
¹³ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁴ Department of Human Genetics, University of Michigan, Ann Arbor, MI, 48019, USA.
¹⁵ School of Electrical and Information Engineering, University of the Witwatersrand, Johannesburg, South Africa.
¹⁶ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Michele.Ramsay@wits.ac.za.
¹⁷ Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Michele.Ramsay@wits.ac.za.

^# Contributed equally.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Africa South of the Sahara
Cholesterol, LDL / genetics
Cross-Sectional Studies
Genome-Wide Association Study*
Humans

Substances

Cholesterol, LDL

Abstract

Publication types

MeSH terms

Substances

Grants and funding