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

Taneera, Jalal LU ; Lang, Stefan LU ; Sharma, Amitabh LU ; Fadista, Joao LU ; Zhou, Yuedan LU ; Ahlqvist, Emma LU ; Jonsson, Anna LU ; Lyssenko, Valeriya LU ; Vikman, Petter LU and Hansson, Ola LU , et al. (2012) In Cell Metabolism 16(1). p.122-134
Abstract
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... (More)
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. (Less)
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publication status
published
subject
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Cell Metabolism
volume
16
issue
1
pages
122 - 134
publisher
Cell Press
external identifiers
  • wos:000306383200016
  • pmid:22768844
  • scopus:84863516095
ISSN
1550-4131
DOI
10.1016/j.cmet.2012.06.006
language
English
LU publication?
yes
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4838cc9f-b937-48a6-a14c-ec1744aa136e (old id 2967377)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22768844?dopt=Abstract
date added to LUP
2012-08-09 16:51:29
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2017-10-29 04:31:02
@article{4838cc9f-b937-48a6-a14c-ec1744aa136e,
  abstract     = {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.},
  author       = {Taneera, Jalal and Lang, Stefan and Sharma, Amitabh and Fadista, Joao and Zhou, Yuedan and Ahlqvist, Emma and Jonsson, Anna and Lyssenko, Valeriya and Vikman, Petter and Hansson, Ola and Parikh, Hemang and Korsgren, Olle and Soni, Arvind and Krus, Ulrika and Zhang, Enming and Jing, Xingjun and Esguerra, Jonathan and Wollheim, Claes and Salehi, S Albert and Rosengren, Anders and Renström, Erik and Groop, Leif},
  issn         = {1550-4131},
  language     = {eng},
  number       = {1},
  pages        = {122--134},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2012.06.006},
  volume       = {16},
  year         = {2012},
}