Genome-wide association study of type 2 diabetes in Africa

Chen, Ji, Sun, Meng, Adeyemo, Adebowale, Pirie, Fraser, Carstensen, Tommy, Pomilla, Cristina, Doumatey, Ayo P, Chen, Guanjie, Young, Elizabeth H, Sandhu, Manjinder
et al (show 7 more authors) (2019) Genome-wide association study of type 2 diabetes in Africa. DIABETOLOGIA, 62 (7). pp. 1204-1211.

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<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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.<h4>Results</h4>The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10<sup>-13</sup>). 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<sup>-9</sup>, 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.<h4>Conclusions/interpretation</h4>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.

Item Type: Article
Uncontrolled Keywords: Africa, Established loci, Fine-mapping, Genome-wide association study, Type 2 diabetes
Depositing User: Symplectic Admin
Date Deposited: 14 May 2019 10:47
Last Modified: 19 Jan 2023 00:45
DOI: 10.1007/s00125-019-4880-7
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