期刊
DIABETOLOGIA
卷 62, 期 7, 页码 1204-1211出版社
SPRINGER
DOI: 10.1007/s00125-019-4880-7
关键词
Africa; Established loci; Fine-mapping; Genome-wide association study; Type 2 diabetes
资金
- Wellcome [090532, 203141, 106130, 098381, 090367, WT206194]
- MRC [G0601261]
- NIH [U01DK105535, R01DK098032, U01DK085545]
- Servier South Africa
- South African Sugar Association
- Victor Daitz Foundation
- Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH)
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Center for Information Technology
- Office of the Director at the National Institutes of Health [1ZIAHG200362]
- MRC [G0601261] Funding Source: UKRI
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIAHG200362] Funding Source: NIH RePORTER
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 x 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 x 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.
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