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. BautistaE. 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, G. Morahan, 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, F. Pociot, 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. Tilmann, 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, N. Bottini, 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, Richard A 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, Jin-Xiong 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, Francesco 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. Rich, 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

Research output: Contribution to journalArticle

1102 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)703-707
Number of pages5
JournalNature Genetics
Volume41
Issue number6
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D. J., Stevens, H., Todd, J. A., Walker, N. M., Rich, S. S., Baskerville, T., ... Zhang, Q. (2009). Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, 41(6), 703-707. https://doi.org/10.1038/ng.381