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

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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

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Type 1 Diabetes Mellitus
Chromosomes
Genome
Genome-Wide Association Study
Autoimmune Diseases
Thyroid Diseases
Single Nucleotide Polymorphism
Case-Control Studies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Todd, J. A., Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., ... 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

Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. / Todd, John A.; Walker, Neil M.; Cooper, Jason D.; Smyth, Deborah J.; Downes, Kate; Plagnol, Vincent; Bailey, Rebecca; Nejentsev, Sergey; Field, Sarah F.; Payne, Felicity; Lowe, Christopher E.; Szeszko, Jeffrey S.; Hafler, Jason P.; Zeitels, Lauren; Yang, Jennie H M; Vella, Adrian; Nutland, Sarah; Stevens, Helen E.; Schuilenburg, Helen; Coleman, Gillian; Maisuria, Meeta; Meadows, William; Smink, Luc J.; Healy, Barry; Burren, Oliver S.; Lam, Alex A C; Ovington, Nigel R.; Allen, James; Adlem, Ellen; Leung, Hin Tak; Wallace, Chris; Howson, Joanna M M; Guja, Cristian; Ionescu-Tîrgovişte, Constantin; Simmonds, Matthew J.; Heward, Joanne M.; Gough, Stephen C L; Dunger, David B.; Wicker, Linda S.; Clayton, David G.

In: Nature Genetics, Vol. 39, No. 7, 07.2007, p. 857-864.

Research output: Contribution to journalArticle

Todd, JA, Walker, NM, Cooper, JD, Smyth, DJ, Downes, K, Plagnol, V, Bailey, R, Nejentsev, S, Field, SF, Payne, F, Lowe, CE, Szeszko, JS, Hafler, JP, Zeitels, L, Yang, JHM, Vella, A, Nutland, S, Stevens, HE, Schuilenburg, H, Coleman, G, Maisuria, M, Meadows, W, Smink, LJ, Healy, B, Burren, OS, Lam, AAC, Ovington, NR, Allen, J, Adlem, E, Leung, HT, Wallace, C, Howson, JMM, Guja, C, Ionescu-Tîrgovişte, C, Simmonds, MJ, Heward, JM, Gough, SCL, Dunger, DB, Wicker, LS & Clayton, DG 2007, 'Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes', Nature Genetics, vol. 39, no. 7, pp. 857-864. https://doi.org/10.1038/ng2068
Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nature Genetics. 2007 Jul;39(7):857-864. https://doi.org/10.1038/ng2068
Todd, John A. ; Walker, Neil M. ; Cooper, Jason D. ; Smyth, Deborah J. ; Downes, Kate ; Plagnol, Vincent ; Bailey, Rebecca ; Nejentsev, Sergey ; Field, Sarah F. ; Payne, Felicity ; Lowe, Christopher E. ; Szeszko, Jeffrey S. ; Hafler, Jason P. ; Zeitels, Lauren ; Yang, Jennie H M ; Vella, Adrian ; Nutland, Sarah ; Stevens, Helen E. ; Schuilenburg, Helen ; Coleman, Gillian ; Maisuria, Meeta ; Meadows, William ; Smink, Luc J. ; Healy, Barry ; Burren, Oliver S. ; Lam, Alex A C ; Ovington, Nigel R. ; Allen, James ; Adlem, Ellen ; Leung, Hin Tak ; Wallace, Chris ; Howson, Joanna M M ; Guja, Cristian ; Ionescu-Tîrgovişte, Constantin ; Simmonds, Matthew J. ; Heward, Joanne M. ; Gough, Stephen C L ; Dunger, David B. ; Wicker, Linda S. ; Clayton, David G. / Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. In: Nature Genetics. 2007 ; Vol. 39, No. 7. pp. 857-864.
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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.",
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AU - Plagnol, Vincent

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AU - Nutland, Sarah

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AU - Maisuria, Meeta

AU - Meadows, William

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AU - Healy, Barry

AU - Burren, Oliver S.

AU - Lam, Alex A C

AU - Ovington, Nigel R.

AU - Allen, James

AU - Adlem, Ellen

AU - Leung, Hin Tak

AU - Wallace, Chris

AU - Howson, Joanna M M

AU - Guja, Cristian

AU - Ionescu-Tîrgovişte, Constantin

AU - Simmonds, Matthew J.

AU - Heward, Joanne M.

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AU - Wicker, Linda S.

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