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Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. We identify a previously-unreported genome-wide significant locus:  ZRANB3  (Zinc Finger RANBP2-Type Containing 3, lead SNP  p  = 2.831 × 10 −9 ). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic β-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine  Zranb3  in  MIN6  β-cells results in impaired insulin secretion in response to high glucose, implicating  Zranb3  in β-cell functional response to high glucose conditions. We also show transferability in our study of 32 established T2D loci. Our findings advance understanding of the genetics of T2D in non-European ancestry populations.

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response