Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P 10 6). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P 0.01; overall P 5 × 10 8) and 4 additional regions provided nominal evidence of replication (P 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.

Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes / J.C. Barrett, D.G. Clayton, P. Concannon, B. Akolkar, J.D. Cooper, H.A. Erlich, C. Julier, G. Morahan, J. Nerup, C. Nierras, V. Plagnol, F. Pociot, H. Schuilenburg, D.J. Smyth, H. Stevens, J.A. Todd, N.M. Walker, S.S. Rich, T. Baskerville, N. Bautista, E. Bhatia, V. Bhatia, K. Bin Hasan, F. Bonnici, T. Brodnicki, F. Cameron, K. Chaichanwatanakul, P.T. Cheung, P. Colman, A. Cotterill, J. Couper, R. Cutfield, T. Davis, P. Dixon, K. Donaghue, K. Dowling, P. Drury, S. Dye, S. Gellert, R. Abdul Ghani, R. Greer, X. Han, L. Harrison, N. Homatopoulos, L. Ji, T. Jones, L.K. Yin, N.A. Kamaruddin, U. Kanga, A. Kanungo, G. Kaur, B. Kek, S. Knowles, J. Krebs, N. Kumar, Y.J. Lee, X. Li, S. Liktimaskul, M. Lloyd, A. Loth, A. Louey, N. Mehra, T. Merriman, L. Min, R. Moses, G. Mraz, R. Murphy, I. Nicholson, A. Panelo, P. Poh, G. Price, N. Ratnam, C. Sanjeevi, S. Sedimbi, S. Shen, G.S. Ying, B. Tait, N. Tandon, A. Thomas, M. Varney, P. Weerakulwattana, J. Willis, L. Albret, F. Ampudia-Blasco, J. Argente, G. Babadjanova, K. Badenhoop, T. Battelino, G. Beilhack, R. Bergholdt, P. Bingley, B. Boehm, J. Bolidson, C. Brorsson, J. Carlson, L. Castano, K. Chandler, O. Cinek, E. Cipponeri, R. Corripio, B. Garcia Cuartero, A. de Leiva, A. Fagulha, M. Fernandez Balcells, C. Guja, P. Gutierrez, E. Hatziagelaki, S. Heath, W. Helmberg, M. Hernandez, I. Holzheu, N. Hosszufalusi, C. Ionescu-Tirgoviste, J. Johannesen, C. Julier, H. Kahles, M. Knip, I. Kockum, E. Kojo, K. Koprivarova, O. Kordonouri, A. Kretowski, D. Krikovszky, A. Kurkhaus, N. Lalic, E. Lavant, A. Long, J. Ludvigsson, L. Madacsy, M. Marga, D. Mauricio, G. Mazurkievicz, J. Nerup, F.J. Novoa Mogollon, M.T. Petersen, M. Phillip, V. Pirags, P. Pozzilli, R. Rappner, B. Roep, S. Rokni, S. Rosinger, O. Rubio-Cabezas, C. Ruckgaber, I. Satman, E. Schober, J. Seufert, R. Sing, J. Skrha, E. Sobngwi, M. Somerville, G. Spinas, V. Tillmann, D. Undlien, V. Urbanavicius, B. Van der Auwera, F. Vasquez San Miguel, A. Vazeo-Gerasimidi, D. Velickiene, A. Wagner, A. Williams, M. Wurzburger, A. Ziegler, M. Agleham, A. Aldrich, R. Alemzadeh, T. Aly, S. Arora, A. Austin, D. Becker, C. Benoist, N. Berka, S. Bhatia, P. Bonella, S. Boyle, B. Brady, W. Brickman, R. Christensen, P. Concannon, R. Couch, D. Counts, J. Crandall, M. Daniels, L. Dolan, D. Donaldson, A. Doria, G. Eisenbarth, R. El-Hajj, H. Erlich, P. Fain, A.L. Fear, R. Ferry, R. Fiallo-Scharer, S. Ghosh, S. Gitelman, M. Godwin, R. Goland, N. Goodman, G. Goodwin, J. Gravely, C. Greenbaum, C. Gudgeon, F. Gunville, W. Hagopian, H. Hakonarson, J. Hansen, K. Harrington, J. Hassing, W. Hilliker, R. Hoffman, E. Hulbert, R. Izquierdo, N. Jospe, K. Kaiserman, F. Kaufman, S. Kim, E. Kloos, R. Kosoy, J. Lane, J. Lane, J. Lawrence, C. Levetan, P. Levin, R. Lipton, J. Lonsdale, V. Magnuson, J. Marks, B. Mayer-Davis, R. Mcevoy, R. Mcindoe, L. Merkle, D. Metzger, D. Miao, E. Mickelson, P. Moonsamy, W. Moore, A. Moran, J. Noble, G. Olsem, S. Onengut-Gumuscu, T. Orban, C. Orlowski, A. Paterson, M. Pietropaolo, C. Pihoker, C. Polychronakos, J. Post, D. Postellon, A. Pugliese, H. Qu, T. Quattrin, M. Rappaport, P. Raskin, H. Risbeck, H. Rodriguez, L. Rodriguez, M. Rogers, B. Russell, D. Schatz, C. Scott, J.X. She, D. Shulman, L. Soyka, P. Speiser, H. Starkman, A. Steck, S. Stender, L. Stratton, D. Sur, S. Taback, K. Thrailkill, E. Toth, P. Trymbiski, E. Tsalikian, K. Vertachnik, J. Wahlen, X. Wang, S. Weber, D. Wherrett, S. Willi, D. Wilson, J. Youkey, N. Young, L. Yu, D. Zimmerman, E. Adlem, J. Allen, J. Brown, O. Burren, P. Clarke, D. Clayton, G. Coleman, J. Cooper, F. Cucca, S. Duley, D. Dunger, V. Everett, M. Hardy, D. Harrison, I. Harrison, S. Hawkins, B. Healy, S. Hood, S. Howell, M. Maisuria, W. Meadows, T. Mistry, S. Nutland, N. Ovington, H. Schuilenburg, A. Simpson, L. Smink, H. Stevens, N. Taylor, J. Todd, J. Tuomilehto, N. Walker, B. Widmer, M. Wilson, H. Withers, M. Brown, W.M. Chen, A. Crews, J. Griffin, M. Hall, T. Harnish, J. Hepler, J. Hilner, N. King, K. Lohman, L. Lu, J. Mychaleckyj, J. Nail, L. Perdue, J. Pierce, D. Reboussin, S. Rushing, M. Sale, E. Sides, B. Snively, H. Teuschler, G. Theil, D. Williams, B. Akolkar, C. Mckeon, C. Nierras, E. Thomson, D. Altshuler, K. Au, S. Bain, L. Barcellos, S. Barral, T. Becker, F. Briggs, P. Bronson, M. Daly, P. de Bakker, P. Deloukas, B. Devlin, M.C. Eike, L. Field, S. Gabriel, N. Garge, S. Gaudieri, B. Goldstein, C. Gorodezky, S. Hamon, C. He, J. Howson, K. Humphreys, I. James, M. Lathrop, B.A. Lie, D. Li, S. Mack, R. Mcginnis, E. Mckinnon, W. Mclaren, D. Nolan, M. Olsson, J. Ott, D. Owerbach, C. Patterson, R. Podolsky, P. Ramsay, V. Rangantah, N. Risch, K.S. Ronningen, X. Shao, R. Single, M. Steffes, G. Thomson, A.M. Valdes, C. Vandiedonck, P. Whittaker, Q. Zhang, N. Bottini. - In: NATURE GENETICS. - ISSN 1061-4036. - 41:6(2009 Jun), pp. 703-707. [10.1038/ng.381]

Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

E. Cipponeri;
2009

Abstract

Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P 10 6). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P 0.01; overall P 5 × 10 8) and 4 additional regions provided nominal evidence of replication (P 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.
Settore MEDS-08/A - Endocrinologia
giu-2009
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