A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2967377
- author
- organization
-
- Translational Muscle Research (research group)
- Diabetes - Cardiovascular Disease (research group)
- Islet cell physiology (research group)
- Diabetes - Islet Patophysiology (research group)
- Diabetes - Islet Cell Exocytosis (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- 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
- id
- 4838cc9f-b937-48a6-a14c-ec1744aa136e (old id 2967377)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22768844?dopt=Abstract
- date added to LUP
- 2016-04-04 08:54:50
- date last changed
- 2024-05-12 01:22:19
@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}}, doi = {{10.1016/j.cmet.2012.06.006}}, volume = {{16}}, year = {{2012}}, }