Untangling the genetics of beta cell dysfunction and death in type 1 diabetes

Catherine C. Robertson; Ruth M. Elgamal; Belle A. Henry-Kanarek; Peter Arvan; Shuibing Chen; Sangeeta Dhawan; Decio L. Eizirik; John S. Kaddis; Golnaz Vahedi; Stephen C.J. Parker; Kyle J. Gaulton; Scott A. Soleimanpour

Molecular Metabolism (Aug 2024)

Untangling the genetics of beta cell dysfunction and death in type 1 diabetes

Catherine C. Robertson,
Ruth M. Elgamal,
Belle A. Henry-Kanarek,
Peter Arvan,
Shuibing Chen,
Sangeeta Dhawan,
Decio L. Eizirik,
John S. Kaddis,
Golnaz Vahedi,
Stephen C.J. Parker,
Kyle J. Gaulton,
Scott A. Soleimanpour

Affiliations

Catherine C. Robertson: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
Ruth M. Elgamal: Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
Belle A. Henry-Kanarek: Department of Internal Medicine and Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA
Peter Arvan: Department of Internal Medicine and Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA
Shuibing Chen: Department of Surgery, Weill Cornell Medicine, New York, NY, USA; Center for Genomic Health, Weill Cornell Medicine, New York, NY, USA
Sangeeta Dhawan: Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA, USA
Decio L. Eizirik: ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium
John S. Kaddis: Department of Diabetes and Cancer Discovery Science, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA
Golnaz Vahedi: Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Stephen C.J. Parker: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA; Corresponding author.
Kyle J. Gaulton: Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Corresponding author.
Scott A. Soleimanpour: Department of Internal Medicine and Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA; Corresponding author. 1000 Wall Street, Brehm Tower Suite 6329, Ann Arbor, MI 48197, USA.

Journal volume & issue: Vol. 86
p. 101973

Abstract

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Background: Type 1 diabetes (T1D) is a complex multi-system disease which arises from both environmental and genetic factors, resulting in the destruction of insulin-producing pancreatic beta cells. Over the past two decades, human genetic studies have provided new insight into the etiology of T1D, including an appreciation for the role of beta cells in their own demise. Scope of Review: Here, we outline models supported by human genetic data for the role of beta cell dysfunction and death in T1D. We highlight the importance of strong evidence linking T1D genetic associations to bona fide candidate genes for mechanistic and therapeutic consideration. To guide rigorous interpretation of genetic associations, we describe molecular profiling approaches, genomic resources, and disease models that may be used to construct variant-to-gene links and to investigate candidate genes and their role in T1D. Major Conclusions: We profile advances in understanding the genetic causes of beta cell dysfunction and death at individual T1D risk loci. We discuss how genetic risk prediction models can be used to address disease heterogeneity. Further, we present areas where investment will be critical for the future use of genetics to address open questions in the development of new treatment and prevention strategies for T1D.

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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