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

Author

Listed:
  • Adebowale A. Adeyemo

    (National Human Genome Research Institute, National Institutes of Health)

  • Norann A. Zaghloul

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Guanjie Chen

    (National Human Genome Research Institute, National Institutes of Health)

  • Ayo P. Doumatey

    (National Human Genome Research Institute, National Institutes of Health)

  • Carmen C. Leitch

    (University of Maryland School of Medicine)

  • Timothy L. Hostelley

    (University of Maryland School of Medicine)

  • Jessica E. Nesmith

    (University of Maryland School of Medicine)

  • Jie Zhou

    (National Human Genome Research Institute, National Institutes of Health)

  • Amy R. Bentley

    (National Human Genome Research Institute, National Institutes of Health)

  • Daniel Shriner

    (National Human Genome Research Institute, National Institutes of Health)

  • Olufemi Fasanmade

    (University of Lagos)

  • Godfrey Okafor

    (University of Nigeria Teaching Hospital)

  • Benjamin Eghan

    (University of Science and Technology)

  • Kofi Agyenim-Boateng

    (University of Science and Technology)

  • Settara Chandrasekharappa

    (National Human Genome Research Institute, National Institutes of Health)

  • Jokotade Adeleye

    (College of Medicine, University of Ibadan)

  • William Balogun

    (College of Medicine, University of Ibadan)

  • Samuel Owusu

    (University of Ghana Medical School)

  • Albert Amoah

    (University of Ghana Medical School)

  • Joseph Acheampong

    (University of Science and Technology)

  • Thomas Johnson

    (University of Lagos)

  • Johnnie Oli

    (University of Nigeria Teaching Hospital)

  • Clement Adebamowo

    (University of Maryland)

  • Francis Collins

    (National Institutes of Health)

  • Georgia Dunston

    (National Human Genome Center at Howard University)

  • Charles N. Rotimi

    (National Human Genome Research Institute, National Institutes of Health)

Abstract

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.

Suggested Citation

  • Adebowale A. Adeyemo & Norann A. Zaghloul & Guanjie Chen & Ayo P. Doumatey & Carmen C. Leitch & Timothy L. Hostelley & Jessica E. Nesmith & Jie Zhou & Amy R. Bentley & Daniel Shriner & Olufemi Fasanma, 2019. "ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10967-7
    DOI: 10.1038/s41467-019-10967-7
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