Recent advances in the genetics of RA susceptibility.
RA is a common autoimmune disease with a complex aetiology in which genetic and environmental factors contribute to disease. The genetic component of RA is largely undefined and, up until very recently, there were only two reproducible associations. The strongest of these associations is of genes within the HLA region, particularly the HLA-DRB1 gene. A second, more modest, association identified has been of the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene. Advances in genotyping technology have facilitated the application of whole genome association approaches to identify disease causal variants. This, coupled with the availability of large case and control collections has enabled the identification of low-to-moderate risk loci. These newer study designs combined with traditional linkage and association studies have accelerated the identification of novel risk loci. The past few months alone have witnessed the identification of three new RA risk loci. In this review, we aim to give an update on recent progress in RA genetics, focusing mainly on the identification of novel loci.
Bowes
J
J
ARC-EU, Stopford Building, University of Manchester, Manchester, UK. j.bowes@manchester.ac.uk
Barton
A
A
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D047990:TNF Receptor-Associated Factor 1; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22