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

Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, 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 AS, , Burton PR, Clayton DG, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Davison D, Easton D, Evans D, Leung HT, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop GM, Connell J, Dominiczak A, Braga Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdóttir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Compston A, Ouwehand NJ, Samani MR, Isaacs JD, Morgan AW, Wilson GD, Ardern-Jones A, Berg J, Brady A, Bradshaw N, Brewer C, Brice G, Bullman B, Campbell J, Castle B, Cetnarsryj R, Chapman C, Chu C, Coates N, Cole T, Davidson R, Donaldson A, Dorkins H, Douglas F, Eccles D, Eeles R, Elmslie F, Evans DG, Goff S, Goodman S, Goudie D, Gray J, Greenhalgh L, Gregory H, Hodgson SV, Homfray T, Houlston RS, Izatt L, Jackson L, Jeffers L, Johnson-Roffey V, Kavalier F, Kirk C, Lalloo F, Langman C, Locke I, Longmuir M, Mackay J, Magee A, Mansour S, Miedzybrodzka Z, Miller J, Morrison P, Murday V, Paterson J, Pichert G, Porteous M, Rahman N, Rogers M, Rowe S, Shanley S, Saggar A, Scott G, Side L, Snadden L, Steel M, Thomas M, Thomas S, McCarthy MI, Hattersley AT

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.

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.

Published 1 June 2007 in Science, 316(5829): 1336-41.
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Diabetes Research Today Archive:

Volume 1 (2004)
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Volume 2 (2005)
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Volume 3 (2006)
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Volume 4 (2007)
  Issue 1 (January)
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  Issue 5 (May)
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  Issue 7 (July)
  Issue 8 (August)
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  Issue 11 (November)
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Volume 5 (2008)
  Issue 1 (January)
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  Issue 3 (March)
  Issue 4 (April)
  Issue 5 (May)
  Issue 6 (June)
  Issue 7 (July)
  Issue 8 (August)
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