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A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets.

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Summary, in English

Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified gene coexpression and protein-protein interaction networks that were strongly associated with islet insulin secretion and HbA(1c). We integrated our data to form a rank list of putative T2D genes, of which CHL1, LRFN2, RASGRP1, and PPM1K were validated in INS-1 cells to influence insulin secretion, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification of genes potentially involved in T2D.

Publishing year

2012

Language

English

Pages

122-134

Publication/Series

Cell Metabolism

Volume

16

Issue

1

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Cardiovascular Disease
  • Islet cell physiology
  • Diabetes - Islet Patophysiology
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1550-4131