GWAS have identified more than 100 susceptibility loci associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. Previous fine mapping of the TNFAIP3 interacting protein 1 (TNIP1) locus identified two independent TNIP1 SLE risk haplotypes that reduced the expression of TNIP1 mRNA and ABIN1 protein. In this work, we characterized eleven non-protein-coding SNPs carried on the H1 haplotype using bioinformatics and molecular approaches such as EMSAs and dual-luciferase expression assays. We discovered that the hypomorphic expression of TNIP1 results from the combined concordant and opposing allelic effects of multiple risk variants carried on the H1 haplotype. Using HiChIP in EBV B cells, we further discovered that the suppressive effect of the TNIP1 risk haplotype extends to neighboring genes within a shared 3D chromatin network.
The details of our study are now published in Arthritis & Rheumatology: Pasula, et al. Arthritis Rheumatol. 2019.