Evidence map›Paper›PMID 40025146›Full record

ArticleDiabetologia2025

Genome-wide association study identifying novel risk variants associated with glycaemic traits in the continental African AWI-Gen cohort.

Vivien J Chebii, Alisha N Wade, Nigel J Crowther, Engelbert A Nonterah, Godfred Agongo, Z Simayi, Palwende R Boua, Isaac Kisiangani, Michèle Ramsay, Ananyo Choudhury and 2 more

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Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Vivien J ChebiiSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. vivien.chebii@wits.ac.za.ORCID http://orcid.org/0000-0002-3382-5856
Alisha N WadeDepartment of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.ORCID http://orcid.org/0000-0002-1158-2523
Nigel J CrowtherDepartment of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID http://orcid.org/0000-0002-5766-1745
Engelbert A NonterahNavrongo Health Research Centre, Ghana Health Service, Navrongo, Ghana.ORCID http://orcid.org/0000-0001-8491-6478
Godfred AgongoDepartment of Biochemistry and Forensic Sciences, School of Chemical and Biochemical Sciences, C.K. Tedam University of Technology and Applied Sciences, Navrongo, Ghana.ORCID http://orcid.org/0000-0002-4218-5424
Z SimayiDepartment of Pathology, Faculty of Health Sciences, University of Limpopo, Polokwane, South Africa.ORCID http://orcid.org/0000-0001-6399-7301
Palwende R BouaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID http://orcid.org/0000-0001-8325-2665
Isaac KisianganiAfrican Population and Health Research Center, Nairobi, Kenya.ORCID http://orcid.org/0000-0002-1107-4334
Michèle RamsaySydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID http://orcid.org/0000-0002-4156-4801
Ananyo ChoudhurySydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Ananyo.Choudhury@wits.ac.za.ORCID http://orcid.org/0000-0001-8225-9531
Dhriti SenguptaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Dhriti.Sengupta@wits.ac.za.ORCID http://orcid.org/0000-0001-6315-7804
as members of the H3Africa AWI-Gen study

Funding

Shared Core: Biobanking, Bioinformatics and Data ManagementU54HG006938 · NHGRI · WITS HEALTH CONSORTIUM (PTY), LTD · PI RAMSAY, MICHELE MICHELE · 2012 to 2022
$12.2M
Department of Science and Technology (now Department of Science and Innovation), South Africa DST/CON 0056/2014NHGRI NIH HHS U54 HG006938NHGRI NIH HHS U54HG006938
6 · The paper itself

Abstract

aims/hypothesisGlycaemic traits such as high fasting glucose levels and insulin resistance are positively associated with the risk of type 2 diabetes and other cardiometabolic diseases. Genetic association studies have identified hundreds of associations for each glycaemic trait, yet very few studies have involved continental African populations. We report the results of genome-wide association studies (GWASs) in a pan-African cohort for four glycaemic traits, namely fasting glucose, fasting insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-B), which are quantitative variables that affect the risk of developing type 2 diabetes.

methodsGWASs for the four traits were conducted in approximately 10,000 individuals from the Africa Wits-INDEPTH Partnership for Genomics Studies (AWI-Gen) cohort, with participants from Burkina Faso, Ghana, Kenya and South Africa. Association testing was performed using linear mixed models implemented in BOLT-LMM, with age, sex, BMI and principal components as covariates. Replication, fine mapping and functional annotation were performed using standard approaches.

resultsWe identified a novel signal (rs574173815) in the intron of the ankyrin repeat domain 33B (ANKRD33B) gene associated with fasting glucose, and a novel signal (rs114029796) in the intronic region of the WD repeat domain 7 (WDR7) gene associated with fasting insulin. SNPs in WDR7 have been shown to be associated with type 2 diabetes. A variant (rs74806991) in the intron of ADAM metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) and another variant (rs6506934) in the β-1,4-galactosyltransferase 6 gene (B4GALT6) are associated with HOMA-IR. Both ADAMTS16 and B4GALT6 are implicated in the development of type 2 diabetes. In addition, our study replicated several well-established fasting glucose signals in the GCK-YTK6, SLC2A2 and THORLNC gene regions. CONCLUSIONS/

interpretationOur findings highlight the importance of performing GWASs for glycaemic traits in under-represented populations, especially continental African populations, to discover novel associated variants and broaden our knowledge of the genetic aetiology of glycaemic traits. The limited replication of well-known signals in this study hints at the possibility of a unique genetic architecture of these traits in African populations. DATA AVAILABILITY: The dataset used in this study is available in the European Genome-Phenome Archive (EGA) database ( https://ega-archive.org/ ) under study accession code EGAS00001002482. The phenotype dataset accession code is EGAD00001006425 and the genotype dataset accession code is EGAD00010001996. The availability of these datasets is subject to controlled access by the Data and Biospecimen Access Committee of the H3Africa Consortium. GWAS summary statistics are accessible through the NHGRI-EBI GWAS Catalog ( https://www.ebi.ac.uk/gwas/ ).

Indexed as

Blood GlucoseDiabetes Mellitus, Type 2AdultBlack PeopleCohort StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulinInsulin ResistanceMaleMiddle AgedPolymorphism, Single NucleotideBlood GlucoseInsulinAfrican ancestryFasting glucoseFasting insulinGWASType 2 diabetes

Identifiers

PMID40025146
PMCPMC12069158

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