Association of NCF2,IKZF1,IRF8,IFIH1,and TYK2 with systemic lupus erythematosus

Systemic lupus erythematosus (sle) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. currently,~8% of the genetic contribution to sle in europeans is known,following publication of several moderate-sized genome-wide (gw) association studies,which identified loci with a strong effect (or&1.3). in order to identify additional genes contributing to sle susceptibility,we conducted a replication study in a uk dataset (870 cases,5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. association analysis in the uk dataset and subsequent meta-analysis with the published data identified five sle susceptibility genes reaching genome-wide levels of significance (p comb<5×10 -8): ncf2 (p comb = 2.87×10 -11),ikzf1 (p comb = 2.33×10 -9),irf8 (p comb = 1.24×10 -8),ifih1 (p comb = 1.63×10 -8),and tyk2 (p comb = 3.88×10 -8). each of the five new loci identified here can be mapped into interferon signalling pathways,which are known to play a key role in the pathogenesis of sle. these results increase the number of established susceptibility genes for lupus to ~30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease. © 2011 cunninghame graham et al.