Combining A Massively Parallel Reporter Assay and Human Data to Elucidate Genetic Mechanisms Driving Risk for...

While progress has been made in identifying the true risk-driving single nucleotide polymorphisms (SNPS) on juvenile idiopathic arthritis (JIA) risk haplotypes, the affected cells and target genes largely remain unknown.

We used data from a previously published massively parallel reporter assay (MPRA) to query human data in the Database of Immune Cell eQTLs (DICE) and the Gene-Tissue Expression (GTEx) database to identify affected cells and target genes of MPRA-identified SNPs in immune cells and relevant tissues.

SNPs identified on MPRA were associated with gene expression levels in a broad range of immune cells in the DICE database, including CD4+ and CD8+ T lymphocytes, monocytes, NK cells, and B cells. MPRA-identified SNPs showed strong associations with gene expression in GTEx whole blood, spleen, and/or EBV-transformed lymphocytes.

Our data show the efficacy of combining MPRA and using human cells/tissue expression data to elucidate complex mechanisms driving genetic risk for JIA.