Letter abstract
Nature Genetics 39, 857 - 864 (2007)
Published online: 6 June 2007 | doi:10.1038/ng2068
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
John A Todd1, Neil M Walker1,9, Jason D Cooper1,9, Deborah J Smyth1,9, Kate Downes1, Vincent Plagnol1, Rebecca Bailey1, Sergey Nejentsev1, Sarah F Field1, Felicity Payne1, Christopher E Lowe1, Jeffrey S Szeszko1, Jason P Hafler1, Lauren Zeitels1, Jennie H M Yang1, Adrian Vella1,8, Sarah Nutland1, Helen E Stevens1, Helen Schuilenburg1, Gillian Coleman1, Meeta Maisuria1, William Meadows1, Luc J Smink1, Barry Healy1, Oliver S Burren1, Alex A C Lam1, Nigel R Ovington1, James Allen1, Ellen Adlem1, Hin-Tak Leung1, Chris Wallace2, Joanna M M Howson1, Cristian Guja3, Constantin Ionescu-Tîrgovişte3, Genetics of Type 1 Diabetes in Finland4, Matthew J Simmonds5, Joanne M Heward5, Stephen C L Gough5, David B Dunger7, the Wellcome Trust Case Control Consortium6, Linda S Wicker1 & David G Clayton1
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan1 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.
- Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
- Department of Clinical Pharmacology, William Harvey Research Institute, Bart's and The London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
- Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Disease 'N. Paulescu', Bucharest 79811, Romania.
- Genetics of Type 1 Diabetes in Finland (GET1FIN), Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland.
- Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK.
- Wellcome Trust Case Control Consortium,
- Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
- Current address: Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
- These authors contributed equally to this work.
Correspondence to: John A Todd1 e-mail: john.todd@cimr.cam.ac.uk
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