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.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Chen J,Sun M,Adeyemo A,Pirie F,Carstensen T,Pomilla C,Doumatey AP,Chen G,Young EH,Sandhu M,Morris AP,Barroso I,McCarthy MI,Mahajan A,Wheeler E,Rotimi CN,Motala AAdoi
10.1007/s00125-019-4880-7subject
Has Abstractpub_date
2019-07-01 00:00:00pages
1204-1211issue
7eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-019-4880-7journal_volume
62pub_type
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