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. 2011 Aug;7(8):e1002216.
doi: 10.1371/journal.pgen.1002216. Epub 2011 Aug 4.

Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases

Vincent Plagnol  1 , Joanna M M Howson, Deborah J Smyth, Neil Walker, Jason P Hafler, Chris Wallace, Helen Stevens, Laura Jackson, Matthew J Simmonds; Type 1 Diabetes Genetics Consortium; Polly J Bingley, Stephen C Gough, John A Todd
Affiliations

Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases

Vincent Plagnol et al. PLoS Genet. 2011 Aug.

Abstract

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A).

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Conflict of interest statement

The authors have declared that no competing interests exist.

References

    1. Savola K, Sabbah E, Kulmala P, Vähäsalo P, Ilonen J, et al. Autoantibodies associated with Type I diabetes mellitus persist after diagnosis in children. Diabetologia. 1998;41:1293–1297. - PubMed
    1. Knip M, Korhonen S, Kulmala P, Veijola R, Reunanen A, et al. Prediction of Type 1 Diabetes in the General Population. Diabetes Care. 2010;33:1206–1212. - PMC - PubMed
    1. Wong S, Wen L, Tang M, Ramanathan M, Visintin I, et al. Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes. 2004;53:2581–2587. - PubMed
    1. Pescovitz M, Greenbaum C, Krause-Steinrauf H, Becker D, Gitelman S, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. The New England journal of medicine. 2009;361:2143–2152. - PMC - PubMed
    1. Silveira P, Grey S. B cells in the spotlight: innocent bystanders or major players in the pathogenesis of type 1 diabetes. Trends in endocrinology and metabolism: TEM. 2006;17:128–135. - PubMed

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