Genome-wide association study of type 2 diabetes in Africa.
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.
['Chen|Ji|J|', 'Sun|Meng|M|', 'Adeyemo|Adebowale|A|', 'Pirie|Fraser|F|', 'Carstensen|Tommy|T|', 'Pomilla|Cristina|C|', 'Doumatey|Ayo P|AP|', 'Chen|Guanjie|G|', 'Young|Elizabeth H|EH|', 'Sandhu|Manjinder|M|', 'Morris|Andrew P|AP|', 'Barroso|Inês|I|', 'McCarthy|Mark I|MI|', 'Mahajan|Anubha|A|', 'Wheeler|Eleanor|E|', 'Rotimi|Charles N|CN|', 'Motala|Ayesha A|AA|']
D044383:Blacks D003924:Diabetes Mellitus, Type 2 D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D060005:Genotyping Techniques D006801:Humans D020641:Polymorphism, Single Nucleotide D058118:Transcription Factor 7-Like 2 Protein D044465:Whites
Genome-wide association study Type 2 diabetes Africa Fine-mapping Established loci