Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic and environmental factors. We carried out a genome-wide association scan and replication study and found an association between SLE and a variant in TNFAIP3 (rs5029939, meta-analysis P = 2.89 x 10(-12), OR = 2.29). We also found evidence of two independent signals near TNFAIP3 associated with SLE, including one previously associated with rheumatoid arthritis (RA). These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA.

Figure 1. A genome-wide association scan in SLE identifies TNFAIP3 as a novel risk locus.

Data represent 311,328 SNP variants genotyped in a total of 431 SLE cases and 2155 controls. Panel A is a graphical representation of the -log₁₀ P values organized by chromosome. Loci with P values below the genome-wide significant threshold of 5 × 10^-8 (indicated by the red line) are noted. Panel B, displays the -log₁₀ of the P value for 25 SNPs genotyped in the GWAS spanning the region of association in 6q23 identified in both RA and SLE. Approximate location of TNFAIP3 in the 300 kb region is indicated above the plot (not to scale). The linkage disequilibrium in the region derived from the GWAS dataset is shown with r² values as indicated. The black line delineates the haplotype associated with SLE in this study.