Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes

John A. Todd, Neil M. Walker, Jason D. Cooper, Deborah J. Smyth, Kate Downes, Vincent Plagnol, Rebecca Bailey, Sergey Nejentsev, Sarah F. Field, Felicity Payne, Christopher E. Lowe, Jeffrey S. Szeszko, Jason P. Hafler, Lauren Zeitels, Jennie H.M. Yang, Adrian Vella, Sarah Nutland, Helen E. Stevens, Helen Schuilenburg, Gillian ColemanMeeta Maisuria, William Meadows, Luc J. Smink, Barry Healy, Oliver S. Burren, Alex A.C. Lam, Nigel R. Ovington, James Allen, Ellen Adlem, Hin Tak Leung, Chris Wallace, Joanna M.M. Howson, Cristian Guja, Constantin Ionescu-Tîrgovişte, Matthew J. Simmonds, Joanne M. Heward, Stephen C.L. Gough, David B. Dunger, Linda S. Wicker, David G. Clayton

Research output: Contribution to journalArticle

1033 Scopus citations

Abstract

The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 × 10-7 between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (Pfollow-up ≤ 1.35 × 10 -9; Poverall ≤ 1.15 × 10-14), leaving eight regions with small effects or false-positive associations. We also obtained evidence for chromosome 18q22 (Poverall = 1.38 × 10-8) from a GWA study of nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten.

Original languageEnglish (US)
Pages (from-to)857-864
Number of pages8
JournalNature Genetics
Volume39
Issue number7
DOIs
StatePublished - Jul 2007

ASJC Scopus subject areas

  • Genetics

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    Todd, J. A., Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., Field, S. F., Payne, F., Lowe, C. E., Szeszko, J. S., Hafler, J. P., Zeitels, L., Yang, J. H. M., Vella, A., Nutland, S., Stevens, H. E., Schuilenburg, H., ... Clayton, D. G. (2007). Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nature Genetics, 39(7), 857-864. https://doi.org/10.1038/ng2068