Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-10967-7
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Funding
- Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH)
- National Human Genome Research Institute (NHGRI)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Center for Information Technology
- Office of the Director at the National Institutes of Health [1ZIAHG200362]
- NIH from the Office of Research on Minority Health [3T37TW00041-03S2]
- NIH [R01DK102001, P30DK072488, T32DK098107, F31DK115179]
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZICHG200346, ZIAHG000024, ZIAHG200362] Funding Source: NIH RePORTER
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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 similar to 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 x 10(-9)). Knockdown or genomic knockout of the zebrafish ortholog results in reduction in pancreatic beta-cell number which we demonstrate to be due to increased apoptosis in islets. siRNA transfection of murine Zranb3 in MIN6 beta-cells results in impaired insulin secretion in response to high glucose, implicating Zranb3 in beta-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.
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