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Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD).We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant.We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 × 10-4). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold.In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

Original publication

DOI

10.1186/ar3139

Type

Journal article

Journal

Arthritis research & therapy

Publication Date

01/2010

Volume

12

Addresses

Arthritis Research UK, Epidemiology Unit, Stopford Building, Oxford Road, The University of Manchester, Manchester M13 9PT, UK. steve.eyre@manchester.ac.uk

Keywords

Yorkshire Early Arthritis Consortium, Biologics in RA Control Consortium, Humans, Arthritis, Rheumatoid, Celiac Disease, Diabetes Mellitus, Type 1, Genetic Predisposition to Disease, GTPase-Activating Proteins, Oligonucleotide Array Sequence Analysis, Genotype, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male