Abstract
Rheumatoid arthritis (RA) is a complex disease, meaning that multiple genetic variants, environmental factors and random events interact to trigger pathological pathways. Although many of these etiological factors have not yet been identified, recent groundbreaking advances have expanded our knowledge about the genetic factors that contribute to RA. Here, we review the most recent findings on the genetic risk factors for RA. First, we give an overview of the genetics of RA and briefly describe the susceptibility loci discovered prior to the availability of genome-wide association studies (GWAS). Second, we focus on the newly discovered RA loci that have arisen from GWAS in populations of European ancestry. Through these studies, the number of established RA susceptibility loci has now grown to 13. Third, we discuss several important issues emerging from GWAS, such as ethnic heterogeneity and shared autoimmunity risk loci. Finally, we discuss what still needs to be accomplished before a more complete picture of the genetic risk to RA can be attained.
Acknowledgements
The authors thank the Arthritis Research Campaign for their support, and acknowledge the NIHR Manchester Biomedical Research Centre.
Financial & competing interests disclosure
This work was supported by the Arthritis Research Campaign (grant reference no. 17552). Gisela Orozco is funded by the European Union (Marie Curie IEF Fellowship PIEF-GA-2009-235662). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.