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.
