Genetics, Genomics, and Proteomics of Sjögren’s Syndrome

Dramatic advances in identifying the genetic basis of many human diseases are transforming our fundamental understanding of etiology and pathogenesis. Over the past decade, large global efforts to characterize sequence variation in the human genome have provided the foundation for this extraordinary progress. Success in mapping disease genes has also been fueled by revolutionary advances in our technical capacity for genotyping and analyzing complex genetic datasets. These advances include the technical capacity for genotyping millions of known variants and have ushered in a new era of powerful, large-scale, and highly successful genome screens for many diseases. Scanning the human genome for association of variants with disease is unbiased and not limited by prior selection of a putative candidate gene for testing. As a result, the genes that are associated with disease can be surprising, oftentimes linking previously unsuspected molecular pathways to numerous disease phenotypes. In many cases, an association may be located between genes and have no known or obvious functional effect. Thus, a dramatic shift in our knowledge of the genetic architecture of human disease is underway. Still, much remains to be learned.