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The first wave of genome-wide association studies across the major chronic inflammatory disorders has been completed and has identified over 100 genome-wide significant loci. There has been a striking degree of overlap for major loci across autoimmune diseases, implicating multiple cytokines and cytokine pathways, notably the interleukin 12/23, IL-10, and TNFa pathways. While the multitude of association signals are, to a large extent, of modest, additive effects, the mosaic of association signals across chronic inflammatory diseases provides important comparative insight.
The precise functional consequences of association signals has not been defined for most loci; however, it is likely that many of these signals modulate RNA expression in a tissue and context specific manner which may best be studied in a comprehensive manner through sequence-based transcriptome analyses. The comparative cytokine pathways implicated across chronic inflammatory disorders may have important implications for therapy; modulation of multiple cytokine pathways may more effectively treat some disorders, such as inflammatory bowel disease.
