@article{fda06c86930c4894822d77dfd37943b2,
title = "No association of multiple type 2 diabetes loci with type 1 diabetes",
abstract = "Aims/hypothesis: We used recently confirmed type 2 diabetes gene regions to investigate the genetic relationship between type 1 and type 2 diabetes, in an average of 7,606 type 1 diabetic individuals and 8,218 controls, providing >80% power to detect effects as small as an OR of 1.11 at a false-positive rate of 0.003. Methods: The single nucleotide polymorphisms (SNPs) with the most convincing evidence of association in 12 type 2 diabetes-associated gene regions, PPARG, CDKAL1, HNF1B, WFS1, SLC30A8, CDKN2A-CDKN2B, IGF2BP2, KCNJ11, TCF7L2, FTO, HHEX-IDE and THADA, were analysed in type 1 diabetes cases and controls. PPARG and HHEX-IDE were additionally tested for association in 3,851 type 1 diabetes families. Tests for interaction with HLA class II genotypes, autoantibody status, sex, and age-at-diagnosis of type 1 diabetes were performed with all 12 gene regions. Results: Only PPARG and HHEX-IDE showed any evidence of association with type 1 diabetes cases and controls (p=0.004 and p=0.003, respectively; p>0.05 for other SNPs). The potential association of PPARG was supported by family analyses (p=0.003; p combined=1.0×10 -4). No SNPs showed evidence of interaction with any covariate (p>0.05). Conclusions/interpretation: We found no convincing genetic link between type 1 and type 2 diabetes. An association of PPARG (rs1801282/Pro12Ala) could be consistent with its known function in inflammation. Hence, our results reinforce evidence suggesting that type 1 diabetes is a disease of the immune system, rather than being due to inherited defects in beta cell function or regeneration or insulin resistance.",
keywords = "Age-at-diagnosis, Association study, Autoantibodies, Genetics, PPARG, SLC30A8, Type 1 diabetes, Type 2 diabetes",
author = "Raj, {S. M.} and Howson, {J. M.M.} and Walker, {N. M.} and Cooper, {J. D.} and Smyth, {D. J.} and Field, {S. F.} and Stevens, {H. E.} and Todd, {J. A.}",
note = "Funding Information: This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Disease (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and JDRF International and supported by U01 DK062418. Funding Information: This work was funded by the Juvenile Diabetes Research Foundation (JDRF) International, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Research Centre. The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (079895). We are grateful for the participation of the type 1 diabetic patients and the control individuals, and especially thank the Human Biological Data Interchange for providing blood samples from the USA multiplex families and Diabetes UK for providing blood samples from the UK multiplex families, the Norwegian Study Group for Childhood Diabetes for providing DNA from Norwegian families (D. Undlien and K R{\o}nningen), GET1FIN (J. Tuomilehto, L. Kinnunen, E. Tuomilehto-Wolf, V. Harjutsalo, and T. Valle) for the provision of Finnish samples, funded by the Academy of Finland, the Sigrid Juselius Foundation, and the JDRF; and D. Savage, C. Patterson, D. Carson and P. Maxwell for providing Northern Irish samples. We would like to thank the Medical Research Council and Wellcome Trust for funding the collection of DNA from the British 1958 Birth Cohort. We are also grateful to C. Eftychi (JDRF/WT Diabetes and Inflammation Laboratory) for her help in genotyping, and P. Bingley (Department of Clinical Science, University of Bristol) for measurement of GAD and IA-2 autoantibodies. DNA control samples were provided by: S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton from the Avon and Longitudinal Study of Parents and Children Laboratory in Bristol and the British 1958 Birth Cohort team. 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. ",
year = "2009",
month = oct,
doi = "10.1007/s00125-009-1391-y",
language = "English (US)",
volume = "52",
pages = "109--116",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",
}
