Plagnol, V and Howson, JMM and Smyth, DJ and Walker, N and Hafler, JP and Wallace, C and Stevens, H and Jackson, L and Simmonds, MJ and Bingley, PJ and Gough, SC and Todd, JA and Type 1 Diabet Genetics Consortium, (2011) Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases. PLOS GENET , 7 (8) , Article e1002216. 10.1371/journal.pgen.1002216.
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).
| Type: | Article |
|---|---|
| Title: | Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases |
| Open access status: | An open access publication |
| DOI: | 10.1371/journal.pgen.1002216 |
| Publisher version: | http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3150451/?tool=pubmed |
| Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS, GENETIC RISK MARKERS, ABO BLOOD GROUPS, BETA-CELL, DISEASE SUSCEPTIBILITY, HELICOBACTER-PYLORI, PERNICIOUS ANEMIA, GASTRIC CARCINOMA, CROHNS-DISEASE, HLA-RISK |
| UCL classification: | UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute |
Archive Staff Only: edit this record