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

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A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. / Taneera, Jalal; Lang, Stefan; Sharma, Amitabh; Fadista, Joao; Zhou, Yuedan; Ahlqvist, Emma; Jonsson, Anna Elisabet; Lyssenko, Valeriya; Vikman, Petter; Hansson, Ola; Parikh, Hemang; Korsgren, Olle; Soni, Arvind; Krus, Ulrika; Zhang, Enming; Jing, Xing-Jun; Esguerra, Jonathan L S; Wollheim, Claes B; Salehi, Albert; Rosengren, Anders; Renström, Erik; Groop, Leif.

In: Cell Metabolism, Vol. 16, No. 1, 03.07.2012, p. 122-34.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Taneera, J, Lang, S, Sharma, A, Fadista, J, Zhou, Y, Ahlqvist, E, Jonsson, AE, Lyssenko, V, Vikman, P, Hansson, O, Parikh, H, Korsgren, O, Soni, A, Krus, U, Zhang, E, Jing, X-J, Esguerra, JLS, Wollheim, CB, Salehi, A, Rosengren, A, Renström, E & Groop, L 2012, 'A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets', Cell Metabolism, vol. 16, no. 1, pp. 122-34. https://doi.org/10.1016/j.cmet.2012.06.006

APA

Taneera, J., Lang, S., Sharma, A., Fadista, J., Zhou, Y., Ahlqvist, E., Jonsson, A. E., Lyssenko, V., Vikman, P., Hansson, O., Parikh, H., Korsgren, O., Soni, A., Krus, U., Zhang, E., Jing, X-J., Esguerra, J. L. S., Wollheim, C. B., Salehi, A., ... Groop, L. (2012). A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. Cell Metabolism, 16(1), 122-34. https://doi.org/10.1016/j.cmet.2012.06.006

Vancouver

Taneera J, Lang S, Sharma A, Fadista J, Zhou Y, Ahlqvist E et al. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. Cell Metabolism. 2012 Jul 3;16(1):122-34. https://doi.org/10.1016/j.cmet.2012.06.006

Author

Taneera, Jalal ; Lang, Stefan ; Sharma, Amitabh ; Fadista, Joao ; Zhou, Yuedan ; Ahlqvist, Emma ; Jonsson, Anna Elisabet ; Lyssenko, Valeriya ; Vikman, Petter ; Hansson, Ola ; Parikh, Hemang ; Korsgren, Olle ; Soni, Arvind ; Krus, Ulrika ; Zhang, Enming ; Jing, Xing-Jun ; Esguerra, Jonathan L S ; Wollheim, Claes B ; Salehi, Albert ; Rosengren, Anders ; Renström, Erik ; Groop, Leif. / A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. In: Cell Metabolism. 2012 ; Vol. 16, No. 1. pp. 122-34.

Bibtex

@article{f12afa1e5c5f44699f892d576eef5be6,
title = "A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets",
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.",
keywords = "Aged, Animals, Case-Control Studies, Cell Line, Diabetes Mellitus, Type 2, Female, Gene Expression Profiling, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Protein Interaction Maps, Rats, Receptors, G-Protein-Coupled, Systems Biology",
author = "Jalal Taneera and Stefan Lang and Amitabh Sharma and Joao Fadista and Yuedan Zhou and Emma Ahlqvist and Jonsson, {Anna Elisabet} and Valeriya Lyssenko and Petter Vikman and Ola Hansson and Hemang Parikh and Olle Korsgren and Arvind Soni and Ulrika Krus and Enming Zhang and Xing-Jun Jing and Esguerra, {Jonathan L S} and Wollheim, {Claes B} and Albert Salehi and Anders Rosengren and Erik Renstr{\"o}m and Leif Groop",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
month = jul,
day = "3",
doi = "10.1016/j.cmet.2012.06.006",
language = "English",
volume = "16",
pages = "122--34",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

AU - Taneera, Jalal

AU - Lang, Stefan

AU - Sharma, Amitabh

AU - Fadista, Joao

AU - Zhou, Yuedan

AU - Ahlqvist, Emma

AU - Jonsson, Anna Elisabet

AU - Lyssenko, Valeriya

AU - Vikman, Petter

AU - Hansson, Ola

AU - Parikh, Hemang

AU - Korsgren, Olle

AU - Soni, Arvind

AU - Krus, Ulrika

AU - Zhang, Enming

AU - Jing, Xing-Jun

AU - Esguerra, Jonathan L S

AU - Wollheim, Claes B

AU - Salehi, Albert

AU - Rosengren, Anders

AU - Renström, Erik

AU - Groop, Leif

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/7/3

Y1 - 2012/7/3

N2 - 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.

AB - 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.

KW - Aged

KW - Animals

KW - Case-Control Studies

KW - Cell Line

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Gene Expression Profiling

KW - Gene Regulatory Networks

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Male

KW - Middle Aged

KW - Oligonucleotide Array Sequence Analysis

KW - Polymorphism, Single Nucleotide

KW - Protein Interaction Maps

KW - Rats

KW - Receptors, G-Protein-Coupled

KW - Systems Biology

U2 - 10.1016/j.cmet.2012.06.006

DO - 10.1016/j.cmet.2012.06.006

M3 - Journal article

C2 - 22768844

VL - 16

SP - 122

EP - 134

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -

ID: 46404026