Genome-wide association studies in Sjögren's syndrome: What do the genes tell us about disease pathogenesis?

The pathogenesis of Sjögren's syndrome (SS) likely involves complex interactions between genes and the environment. While the candidate gene approach has been previously used to identify several genes associated with SS, two recent large-scale genome-wide association studies (GWAS) have implicated many more loci as genetic risk factors. Of particular relevance, was the significant association of SS with additional immune-related genes including IL12A, BLK, and CXCR5. GWAS has also uncovered other loci and suggestive gene associations in SS, but none are related to genes encoding salivary or lacrimal components, secretion machinery and neuronal proteins involved in innervations of the glands, respectively. In this review, we discuss these genetic findings with particular attention paid to the genes identified, the strength of associations, and how the SS-associated genes compare to what has been discovered previously in systemic lupus erythematosus (SLE). We also summarize the potential impact of these associated gene products on NFκB and immune pathways and describe how this new information might be integrated further for identifying clinical subsets and understanding the pathogenesis of SS.