دورية أكاديمية
Genome-wide association study of type 2 diabetes in Africa.
| العنوان: | Genome-wide association study of type 2 diabetes in Africa. |
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| المؤلفون: | Chen, Ji, Sun, Meng, Adeyemo, Adebowale, Pirie, Fraser, Carstensen, Tommy, Pomilla, Cristina, Doumatey, Ayo P, Chen, Guanjie, Young, Elizabeth H, Sandhu, Manjinder, Morris, Andrew P, Barroso, Inês, McCarthy, Mark I, Mahajan, Anubha, Wheeler, Eleanor, Rotimi, Charles N, Motala, Ayesha A |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1007/s00125-019-4880-7 Diabetologia |
| سنة النشر: | 2019 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Africa, Established loci, Fine-mapping, Genome-wide association study, Type 2 diabetes, Black People, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein, White People |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/294957Test |
| DOI: | 10.17863/CAM.42044 |
| الإتاحة: | https://doi.org/10.17863/CAM.42044Test https://www.repository.cam.ac.uk/handle/1810/294957Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.7ED5C583 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.42044 |
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