@article{c89f77ca67a847fcb2e6e3c0639d2c89,
title = "Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes",
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.",
author = "Todd, {John A.} and Walker, {Neil M.} and Cooper, {Jason D.} and Smyth, {Deborah J.} and Kate Downes and Vincent Plagnol and Rebecca Bailey and Sergey Nejentsev and Field, {Sarah F.} and Felicity Payne and Lowe, {Christopher E.} and Szeszko, {Jeffrey S.} and Hafler, {Jason P.} and Lauren Zeitels and Yang, {Jennie H.M.} and Adrian Vella and Sarah Nutland and Stevens, {Helen E.} and Helen Schuilenburg and Gillian Coleman and Meeta Maisuria and William Meadows and Smink, {Luc J.} and Barry Healy and Burren, {Oliver S.} and Lam, {Alex A.C.} and Ovington, {Nigel R.} and James Allen and Ellen Adlem and Leung, {Hin Tak} and Chris Wallace and Howson, {Joanna M.M.} and Cristian Guja and Constantin Ionescu-T{\^i}rgovi{\c s}te and Simmonds, {Matthew J.} and Heward, {Joanne M.} and Gough, {Stephen C.L.} and Dunger, {David B.} and Wicker, {Linda S.} and Clayton, {David G.}",
note = "Funding Information: This work was funded by the Juvenile Diabetes Research Foundation International and the Wellcome Trust. We gratefully acknowledge the participation of all the patients, control subjects and family members and thank the Human Biological Data Interchange and Diabetes UK for the USA and UK multiplex families, respectively, the Norwegian Study Group for Childhood Diabetes for the collection of Norwegian families (D. Undlien and K. R{\o}nningen), D. Savage, C. Patterson, D. Carson and P. Maxwell for the Northern Irish samples. GET1FIN (J. Tuomilehto, L. Kinnunen, E. Tuomilehto-Wolf, V. Harjutsalo and T. Valle) thank the Academy of Finland, the Sigrid Juselius Foundation and the JDRF for funding. We acknowledge use of the DNA from the 1958 British Birth Cohort collection, funded by the Medical Research Council and Wellcome Trust, and we thank D. Strachan and P. Burton for their help. We also thank The Avon Longitudinal Study of Parents and Children laboratory in Bristol, including S. Ring, R. Jones, M. Pembrey and W. McArdle for preparing and providing the control DNA samples. We thank colleagues at Affymetrix for help and advice in genotyping and T. Willis, M. Faham and P. Hardenbol for the molecular inversion probe technology. We thank the Wellcome Trust for funding the AITD UK national collection; all doctors and nurses in Birmingham, Bournemouth, Cambridge, Cardiff, Exeter, Leeds, Newcastle and Sheffield for recruitment of patients and J. Franklyn, S. Pearce (Newcastle) and P. Newby (Birmingham) for preparing and providing DNA samples on Graves{\textquoteright} disease patients. We thank V. Everett, G. Scholz and G. Dolman for information technology support. T1D DNA samples were prepared by K. Bourget, S. Duley, M. Hardy, S. Hawkins, S. Hood, E. King, T. Mistry, A. Simpson, S. Wood, P. Lauder, S. Clayton, F. Wright and C. Collins. We thank L. Peterson for helpful discussions. C.W. is supported by the British Heart Foundation. S. Nejentsev is a Diabetes Research and Wellness Foundation Non-Clinical Fellow.",
year = "2007",
month = jul,
doi = "10.1038/ng2068",
language = "English (US)",
volume = "39",
pages = "857--864",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",
}