Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

Eleftheria Zeggini; Michael N. Weedon; Cecilia M. Lindgren; Timothy M. Frayling; Katherine S. Elliott; Hana Lango; Nicholas J. Timpson; John R. B. Perry; Nigel W. Rayner; Rachel M. Freathy; Jeffrey C. Barrett; Beverley Shields; Andrew P. Morris; Sian Ellard; Christopher J. Groves; Lorna W. Harries; Jonathan L. Marchini; Katharine R. Owen; Beatrice Knight; Lon R. Cardon; Mark Walker; Graham A. Hitman; Andrew D. Morris; Alex S. F. Doney; Andrew T. Hattersley; Wellcome Trust Case Control Consortium; Mark I. McCarthy

doi:10.1126/science.1142364

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

Eleftheria Zeggini, Michael N. Weedon, Cecilia M. Lindgren, Timothy M. Frayling, Katherine S. Elliott, Hana Lango, Nicholas J. Timpson, John R. B. Perry, Nigel W. Rayner, Rachel M. Freathy, Jeffrey C. Barrett, Beverley Shields, Andrew P. Morris, Sian Ellard, Christopher J. Groves, Lorna W. Harries, Jonathan L. Marchini, Katharine R. Owen, Beatrice Knight, Lon R. CardonMark Walker, Graham A. Hitman, Andrew D. Morris, Alex S. F. Doney, Andrew T. Hattersley, Wellcome Trust Case Control Consortium, Mark I. McCarthy

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Abstract

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

Original language	English
Pages (from-to)	1336-1341
Number of pages	6
Journal	Science
Volume	316
Issue number	5829
DOIs	https://doi.org/10.1126/science.1142364
Publication status	Published - Jun 2007

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Zeggini, E., Weedon, M. N., Lindgren, C. M., Frayling, T. M., Elliott, K. S., Lango, H., Timpson, N. J., Perry, J. R. B., Rayner, N. W., Freathy, R. M., Barrett, J. C., Shields, B., Morris, A. P., Ellard, S., Groves, C. J., Harries, L. W., Marchini, J. L., Owen, K. R., Knight, B., ... McCarthy, M. I. (2007). Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science, 316(5829), 1336-1341. https://doi.org/10.1126/science.1142364

@article{51b8ef7798b040e2a4989685f1cb1b7b,

title = "Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes",

abstract = "The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.",

author = "Eleftheria Zeggini and Weedon, {Michael N.} and Lindgren, {Cecilia M.} and Frayling, {Timothy M.} and Elliott, {Katherine S.} and Hana Lango and Timpson, {Nicholas J.} and Perry, {John R. B.} and Rayner, {Nigel W.} and Freathy, {Rachel M.} and Barrett, {Jeffrey C.} and Beverley Shields and Morris, {Andrew P.} and Sian Ellard and Groves, {Christopher J.} and Harries, {Lorna W.} and Marchini, {Jonathan L.} and Owen, {Katharine R.} and Beatrice Knight and Cardon, {Lon R.} and Mark Walker and Hitman, {Graham A.} and Morris, {Andrew D.} and Doney, {Alex S. F.} and Hattersley, {Andrew T.} and {Wellcome Trust Case Control Consortium} and McCarthy, {Mark I.}",

note = "dc.publisher: American Association for the Advancement of Science ",

year = "2007",

month = jun,

doi = "10.1126/science.1142364",

language = "English",

volume = "316",

pages = "1336--1341",

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issn = "0036-8075",

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Zeggini, E, Weedon, MN, Lindgren, CM, Frayling, TM, Elliott, KS, Lango, H, Timpson, NJ, Perry, JRB, Rayner, NW, Freathy, RM, Barrett, JC, Shields, B, Morris, AP, Ellard, S, Groves, CJ, Harries, LW, Marchini, JL, Owen, KR, Knight, B, Cardon, LR, Walker, M, Hitman, GA, Morris, AD, Doney, ASF, Hattersley, AT, Wellcome Trust Case Control Consortium & McCarthy, MI 2007, 'Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes', Science, vol. 316, no. 5829, pp. 1336-1341. https://doi.org/10.1126/science.1142364

TY - JOUR

T1 - Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

AU - Zeggini, Eleftheria

AU - Weedon, Michael N.

AU - Lindgren, Cecilia M.

AU - Frayling, Timothy M.

AU - Elliott, Katherine S.

AU - Lango, Hana

AU - Timpson, Nicholas J.

AU - Perry, John R. B.

AU - Rayner, Nigel W.

AU - Freathy, Rachel M.

AU - Barrett, Jeffrey C.

AU - Shields, Beverley

AU - Morris, Andrew P.

AU - Ellard, Sian

AU - Groves, Christopher J.

AU - Harries, Lorna W.

AU - Marchini, Jonathan L.

AU - Owen, Katharine R.

AU - Knight, Beatrice

AU - Cardon, Lon R.

AU - Walker, Mark

AU - Hitman, Graham A.

AU - Morris, Andrew D.

AU - Doney, Alex S. F.

AU - Hattersley, Andrew T.

AU - Wellcome Trust Case Control Consortium

AU - McCarthy, Mark I.

N1 - dc.publisher: American Association for the Advancement of Science

PY - 2007/6

Y1 - 2007/6

N2 - The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

AB - The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.

U2 - 10.1126/science.1142364

DO - 10.1126/science.1142364

M3 - Article

SN - 0036-8075

VL - 316

SP - 1336

EP - 1341

JO - Science

JF - Science

IS - 5829

ER -

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

Abstract

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