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The Genetic Contribution to Type 1 Diabetes

  • Genetics (AP Morris, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To provide an updated summary of discoveries made to date resulting from genome-wide association study (GWAS) and sequencing studies, and to discuss the latest loci added to the growing repertoire of genetic signals predisposing to type 1 diabetes (T1D).

Recent Findings

Genetic studies have identified over 60 loci associated with T1D susceptibility. GWAS alone does not specifically inform on underlying mechanisms, but in combination with other sequencing and omics-data, advances are being made in our understanding of T1D genetic etiology and pathogenesis. Current knowledge indicates that genetic variation operating in both pancreatic β cells and in immune cells is central in mediating T1D risk.

Summary

One of the main challenges is to determine how these recently discovered GWAS-implicated variants affect the expression and function of gene products. Once we understand the mechanism of action for disease-causing variants, we will be well placed to apply targeted genomic approaches to impede the premature activation of the immune system in an effort to ultimately prevent the onset of T1D.

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Funding

This work was supported by an Institute Development Award to the Center for Applied Genomics from the Children’s Hospital of Philadelphia and by the Endowed Chair in Genomic Research to Dr. Hakonarson. Dr. Grant is funded by the Daniel B. Burke Endowed Chair for Diabetes Research, and by NIH grant R01 DK085212.

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Authors and Affiliations

  1. The Center for Applied Genomics, Division of Human Genetics, The Children’s Hospital of Philadelphia, 3615 Civic Center Boulevard, Abramson Research Center, Suite 1216B, Philadelphia, PA, 19104-4318, USA

    Marina Bakay, Rahul Pandey, Struan F.A. Grant & Hakon Hakonarson

  2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Struan F.A. Grant & Hakon Hakonarson

  3. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Struan F.A. Grant

  4. Center for Spatial and Functional Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Struan F.A. Grant

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  1. Marina Bakay
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  2. Rahul Pandey
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  3. Struan F.A. Grant
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  4. Hakon Hakonarson
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Correspondence to Hakon Hakonarson.

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Conflict of Interest

Marina Bakay and Rahul Pandey report they have a patent pending on new innovative weight reduction therapies targeting CLEC16A.

Struan F.A. grant reports he has a patent issue on genetic alterations and methods of use thereof for the diagnosis and treatment of type I diabetes issued (patent number 10125395); a patent issued on genetic alterations on chromosome 16 and methods of use thereof for the diagnosis and treatment of type 1 diabetes (patent number 10266896); and a patent issued on genetic alterations on chromosomes 21Q, 6Q, and 15Q and methods of use thereof for the diagnosis and treatment of type 1 diabetes (patent number 10066266).

Hakon Hakonarson reports he has a patent issued on genetic alterations and methods of use thereof for the diagnosis and treatment of type I diabetes issued (patent number 10125395); a patent issued on genetic alterations on chromosome 16 and methods of use thereof for the diagnosis and treatment of type 1 diabetes issued (patent number 10266896); a patent issued on genetic alterations on chromosomes 21Q, 6Q, and 15Q and methods of use thereof for the diagnosis and treatment of type 1 diabetes (patent number 10066266); and a patent pending on new innovative weight reduction therapies targeting CLEC16A.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Bakay, M., Pandey, R., Grant, S.F. et al. The Genetic Contribution to Type 1 Diabetes. Curr Diab Rep 19, 116 (2019). https://doi.org/10.1007/s11892-019-1235-1

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