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

Andrew P Morris; Benjamin F Voight; Tanya M Teslovich; Teresa Ferreira; Ayellet V Segrè; Valgerdur Steinthorsdottir; Rona J Strawbridge; Abid 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 Müller-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; Anna Elisabet Jonsson; Lars Lind; Inger Njølstad; Wellcome Trust Case Control Consortium

doi:10.1038/ng.2383

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

Andrew P Morris, Benjamin F Voight, Tanya M Teslovich, Teresa Ferreira, Ayellet V Segrè, Valgerdur Steinthorsdottir, Rona J Strawbridge, Abid 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 LuanCecilia M Lindgren, Martina Müller-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, Anna Elisabet Jonsson, Lars Lind, Inger Njølstad, Wellcome Trust Case Control Consortium

SUND Ph.d. skole studieafgift

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

1571 Citationer (Scopus)

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. Genome-wide 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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	44
Udgave nummer	9
Sider (fra-til)	981-90
Antal sider	10
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.2383
Status	Udgivet - sep. 2012

Adgang til dokumentet

10.1038/ng.2383

Citationsformater

Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, A. H., Grallert, H., Mahajan, A., Prokopenko, I., Kang, H. M., Dina, C., Esko, T., Fraser, R. M., Kanoni, S., Kumar, A., Lagou, V., Langenberg, C., ... Wellcome Trust Case Control Consortium (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-90. https://doi.org/10.1038/ng.2383

Morris, AP, Voight, BF, Teslovich, TM, Ferreira, T, Segrè, AV, Steinthorsdottir, V, Strawbridge, RJ, Khan, AH, 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, Müller-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, Jonsson, AE, Lind, L, Njølstad, I & Wellcome Trust Case Control Consortium 2012, 'Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes', Nature Genetics, bind 44, nr. 9, s. 981-90. https://doi.org/10.1038/ng.2383

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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. Genome-wide 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.",

keywords = "Case-Control Studies, Diabetes Mellitus, Type 2, Female, Genes, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Pakistan, Polymorphism, Single Nucleotide, Sex Factors",

author = "Morris, {Andrew P} and Voight, {Benjamin F} and Teslovich, {Tanya M} and Teresa Ferreira and Segr{\`e}, {Ayellet V} and Valgerdur Steinthorsdottir and Strawbridge, {Rona J} and Khan, {Abid Hassan} 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 M{\"u}ller-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 Jonsson, {Anna Elisabet} and Lars Lind and Inger Nj{\o}lstad and {Wellcome Trust Case Control Consortium}",

year = "2012",

month = sep,

doi = "10.1038/ng.2383",

language = "English",

volume = "44",

pages = "981--90",

journal = "Nature Genetics",

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T1 - Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

AU - Morris, Andrew P

AU - Voight, Benjamin F

AU - Teslovich, Tanya M

AU - Ferreira, Teresa

AU - Segrè, Ayellet V

AU - Steinthorsdottir, Valgerdur

AU - Strawbridge, Rona J

AU - Khan, Abid 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 - Müller-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 - Jonsson, Anna Elisabet

AU - Lind, Lars

AU - Njølstad, Inger

AU - Wellcome Trust Case Control Consortium

PY - 2012/9

Y1 - 2012/9

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. Genome-wide 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. Genome-wide 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.

KW - Case-Control Studies

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genes

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Pakistan

KW - Polymorphism, Single Nucleotide

KW - Sex Factors

U2 - 10.1038/ng.2383

DO - 10.1038/ng.2383

M3 - Journal article

C2 - 22885922

SN - 1061-4036

VL - 44

SP - 981

EP - 990

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -