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Genome-wide association study of type 2 diabetes in Africa.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Chen, Ji 
Sun, Meng 
Adeyemo, Adebowale 
Pirie, Fraser 
Carstensen, Tommy 

Abstract

AIMS/HYPOTHESIS: Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations. METHODS: We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Likely causal variants were identified using fine-mapping approaches. RESULTS: The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10-13). Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147). We also detected one novel signal, rs73284431, near AGMO (p = 5.2 × 10-9, minor allele frequency [MAF] = 0.095; monomorphic in most non-African populations), distinct from previously reported signals in the region. In analyses focused on 100 published type 2 diabetes risk loci, we identified 21 with shared causal variants in African and non-African populations. CONCLUSIONS/INTERPRETATION: These results demonstrate the value of performing GWAS in Africans, provide a resource to larger consortia for further discovery and fine-mapping and indicate that additional large-scale efforts in Africa are warranted to gain further insight in to the genetic architecture of type 2 diabetes.

Description

Keywords

Africa, Established loci, Fine-mapping, Genome-wide association study, Type 2 diabetes, Black People, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein, White People

Journal Title

Diabetologia

Conference Name

Journal ISSN

0012-186X
1432-0428

Volume Title

62

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/K013491/1)
Wellcome Trust (via University of KwaZulu-Natal) (CON3161 H3)