Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Wellcome Trust Case Control Consortium; MAGIC Investigators; GIANT Consortium; Andrew P. Morris; Benjamin F. Voight; Tanya M. Teslovich; Teresa Ferreira; Ayellet V. Segre; Valgerdur Steinthorsdottir; Rona J. Strawbridge; Hassan Khan; Harald Grallert; Anubha Mahajan; Inga Prokopenko; Hyun Min Kang; Christian Dina; Tonu Esko; Ross M. Fraser; Stavroula Kanoni; Ashish Kumar; Vasiliki Lagou; Claudia Langenberg; Jian'an Luan; Cecilia M. Lindgren; Martina Mueller-Nurasyid; Sonali Pechlivanis; N. William Rayner; Laura J. Scott; Steven Wiltshire; Loic Yengo; Leena Kinnunen; Elizabeth J. Rossin; Soumya Raychaudhuri; Andrew D. Johnson; Antigone S. Dimas; Ruth J. F. Loos; Sailaja Vedantam; Han Chen; Jose C. Florez; Caroline Fox; Ching-Ti Liu; Denis Rybin; David J. Couper; Wen Hong L. Kao; Man Li; Marilyn C. Cornelis; Peter Kraft; Qi Sun; Rob M. van Dam; Heather M. Stringham; Alex S. F. Doney; Colin N. A. Palmer; Andrew D. Morris; South Asian Type 2 Diabetes SAT2D Consortium

doi:10.1038/ng.2383

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Wellcome Trust Case Control Consortium, MAGIC Investigators, GIANT Consortium, , Andrew P. Morris, Benjamin F. Voight, Tanya M. Teslovich, Teresa Ferreira, Ayellet V. Segre, Valgerdur Steinthorsdottir, Rona J. Strawbridge, Hassan Khan, Harald Grallert, Anubha Mahajan, Inga Prokopenko, Hyun Min Kang, Christian Dina, Tonu Esko, Ross M. FraserStavroula Kanoni, Ashish Kumar, Vasiliki Lagou, Claudia Langenberg, Jian'an Luan, Cecilia M. Lindgren, Martina Mueller-Nurasyid, Sonali Pechlivanis, N. William Rayner, Laura J. Scott, Steven Wiltshire, Loic Yengo, Leena Kinnunen, Elizabeth J. Rossin, Soumya Raychaudhuri, Andrew D. Johnson, Antigone S. Dimas, Ruth J. F. Loos, Sailaja Vedantam, Han Chen, Jose C. Florez, Caroline Fox, Ching-Ti Liu, Denis Rybin, David J. Couper, Wen Hong L. Kao, Man Li, Marilyn C. Cornelis, Peter Kraft, Qi Sun, Rob M. van Dam, Heather M. Stringham, Alex S. F. Doney, Colin N. A. Palmer, Andrew D. Morris, South Asian Type 2 Diabetes SAT2D Consortium

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Abstract

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

Original language	English
Pages (from-to)	981-990
Number of pages	12
Journal	Nature Genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2383
Publication status	Published - Sept 2012

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10.1038/ng.2383

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DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Wellcome Trust Case Control Consortium, MAGIC Investigators, GIANT Consortium, Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segre, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., Mahajan, A., Prokopenko, I., Kang, H. M., Dina, C., Esko, T., ... South Asian Type 2 Diabetes SAT2D Consortium (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-990. https://doi.org/10.1038/ng.2383

@article{5532ec264f1045a39d28d8799c3ec3f2,

title = "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes",

abstract = "To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.",

author = "{DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium} and {Wellcome Trust Case Control Consortium} and {MAGIC Investigators} and {GIANT Consortium} and Morris, {Andrew P.} and Voight, {Benjamin F.} and Teslovich, {Tanya M.} and Teresa Ferreira and Segre, {Ayellet V.} and Valgerdur Steinthorsdottir and Strawbridge, {Rona J.} and Hassan Khan and Harald Grallert and Anubha Mahajan and Inga Prokopenko and Kang, {Hyun Min} and Christian Dina and Tonu Esko and Fraser, {Ross M.} and Stavroula Kanoni and Ashish Kumar and Vasiliki Lagou and Claudia Langenberg and Jian'an Luan and Lindgren, {Cecilia M.} and Martina Mueller-Nurasyid and Sonali Pechlivanis and Rayner, {N. William} and Scott, {Laura J.} and Steven Wiltshire and Loic Yengo and Leena Kinnunen and Rossin, {Elizabeth J.} and Soumya Raychaudhuri and Johnson, {Andrew D.} and Dimas, {Antigone S.} and Loos, {Ruth J. F.} and Sailaja Vedantam and Han Chen and Florez, {Jose C.} and Caroline Fox and Ching-Ti Liu and Denis Rybin and Couper, {David J.} and Kao, {Wen Hong L.} and Man Li and Cornelis, {Marilyn C.} and Peter Kraft and Qi Sun and {van Dam}, {Rob M.} and Stringham, {Heather M.} and Doney, {Alex S. F.} and Palmer, {Colin N. A.} and Morris, {Andrew D.} and {South Asian Type 2 Diabetes SAT2D Consortium}",

year = "2012",

month = sep,

doi = "10.1038/ng.2383",

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pages = "981--990",

journal = "Nature Genetics",

issn = "1061-4036",

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DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Wellcome Trust Case Control Consortium, MAGIC Investigators, GIANT Consortium, Morris, AP, Voight, BF, Teslovich, TM, Ferreira, T, Segre, AV, Steinthorsdottir, V, Strawbridge, RJ, Khan, H, Grallert, H, Mahajan, A, Prokopenko, I, Kang, HM, Dina, C, Esko, T, Fraser, RM, Kanoni, S, Kumar, A, Lagou, V, Langenberg, C, Luan, J, Lindgren, CM, Mueller-Nurasyid, M, Pechlivanis, S, Rayner, NW, Scott, LJ, Wiltshire, S, Yengo, L, Kinnunen, L, Rossin, EJ, Raychaudhuri, S, Johnson, AD, Dimas, AS, Loos, RJF, Vedantam, S, Chen, H, Florez, JC, Fox, C, Liu, C-T, Rybin, D, Couper, DJ, Kao, WHL, Li, M, Cornelis, MC, Kraft, P, Sun, Q, van Dam, RM, Stringham, HM, Doney, ASF , Palmer, CNA & Morris, AD & South Asian Type 2 Diabetes SAT2D Consortium 2012, 'Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes', Nature Genetics, vol. 44, no. 9, pp. 981-990. https://doi.org/10.1038/ng.2383

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. / DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Wellcome Trust Case Control Consortium; MAGIC Investigators et al.
In: Nature Genetics, Vol. 44, No. 9, 09.2012, p. 981-990.

Research output: Contribution to journal › Article › peer-review

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AU - GIANT Consortium

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AU - Steinthorsdottir, Valgerdur

AU - Strawbridge, Rona J.

AU - Khan, Hassan

AU - Grallert, Harald

AU - Mahajan, Anubha

AU - Prokopenko, Inga

AU - Kang, Hyun Min

AU - Dina, Christian

AU - Esko, Tonu

AU - Fraser, Ross M.

AU - Kanoni, Stavroula

AU - Kumar, Ashish

AU - Lagou, Vasiliki

AU - Langenberg, Claudia

AU - Luan, Jian'an

AU - Lindgren, Cecilia M.

AU - Mueller-Nurasyid, Martina

AU - Pechlivanis, Sonali

AU - Rayner, N. William

AU - Scott, Laura J.

AU - Wiltshire, Steven

AU - Yengo, Loic

AU - Kinnunen, Leena

AU - Rossin, Elizabeth J.

AU - Raychaudhuri, Soumya

AU - Johnson, Andrew D.

AU - Dimas, Antigone S.

AU - Loos, Ruth J. F.

AU - Vedantam, Sailaja

AU - Chen, Han

AU - Florez, Jose C.

AU - Fox, Caroline

AU - Liu, Ching-Ti

AU - Rybin, Denis

AU - Couper, David J.

AU - Kao, Wen Hong L.

AU - Li, Man

AU - Cornelis, Marilyn C.

AU - Kraft, Peter

AU - Sun, Qi

AU - van Dam, Rob M.

AU - Stringham, Heather M.

AU - Doney, Alex S. F.

AU - Palmer, Colin N. A.

AU - Morris, Andrew D.

AU - South Asian Type 2 Diabetes SAT2D Consortium

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N2 - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

AB - To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

U2 - 10.1038/ng.2383

DO - 10.1038/ng.2383

M3 - Article

C2 - 22885922

SN - 1061-4036

VL - 44

SP - 981

EP - 990

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Abstract

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