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

Plagnol, Vincent, Howson, Joanna M. M., Smyth, Deborah J. , Walker, Neil, Hafler, Jason P., Wallace, Chris, Stevens, Helen, Jackson, Laura, Simmonds, Matthew J., T1D Genetics Consortium, -, Bingley, Polly J., Gough, Stephen C. and Todd, John A. (2011) Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genetics, 7 (8). ISSN 1553-7390

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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). © 2011 Plagnol et al.

Keywords:autoantibody, cell antigen, glutamate decarboxylase, insulinoma association antigen 2, pancreas islet cell antibody, thyroid peroxidase antibody, unclassified drug, FCRL1 protein, human, FCRL3 protein, human, immunoglobulin receptor, membrane protein, adolescent, article, BACH2 gene, child, chromosome 9q, controlled study, CTLA4 gene, disease association, FCLR3 gene, gastritis, gene, gene frequency, gene locus, genetic association, genetic variability, genome analysis, genotype, Graves disease, human, IFIH1 gene, IL2 gene, IL27 insulinoma associated antigen 2 gene, IL2RA gene, insulin dependent diabetes mellitus, major clinical study, PCA gene, preschool child, promoter region, PTPN22 gene, RASGRP1 gene, SH2B3 gene, single nucleotide polymorphism, STAT4 gene, stomach parietal cell, UBASH3A gene, blood group ABO system, chromosome 1, chromosome 9, genetics, immunology, ABO Blood-Group System, Adolescent, Autoantibodies, Child, Preschool, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 9, Diabetes Mellitus, Type 1, Genome-Wide Association Study, Humans, Membrane Proteins, Polymorphism, Single Nucleotide, Receptors, Immunologic
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22604
Deposited On:01 Apr 2016 09:16

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