Genetic Association of Sjögren's Syndrome

Principal Investigator: John Harley, MD, PhD

Abstract:

We propose to identify the genes that confer risk for Sjögren's syndrome. For the past ten years we have been using the advances of the genomic revolution to pursue the genes that predispose to systemic lupus erythematosus. At this juncture we have identified more than 20 convincing genetic effects for lupus. Now a decade after starting the lupus genetics studies, we are ready to begin work with Sjögren's syndrome, a closely related disorder. Our progress with Sjögren's syndrome will be accelerated because of the infrastructure available and our experience with lupus. We plan to build the scientific organization that will allow us to evaluate 100 candidate genes for genetic association in 300 Sjögren's syndrome patients, their families, and matched controls. In hopes of concentrating our effort on a more genetically homogeneous phenotype we will use the new European-American consensus criteria for primary Sjogren's syndrome, with the added requirement that all affecteds evaluated have anti-Ro autoantibodies. We propose to use a genetic association approach in an experimental design that will lead to gene identification by the following experimental steps: assembling the materials from probands, family members and controls; constructing the clinical and demographic database; and genotyping at candidate genes. Our longer term goal is to perform a reasonably powered genome scan for genetic association, but the technologies and methodologies are not yet proven to be practical for this. Using current genomic infrastructure, the genome scan would extend well beyond the funding period allowed under this R01, and consequently, we envision a commitment to this scientific problem over the next decade, as may be required. To elucidate the genetic component of the etiology of Sjögren's syndrome would provide important new insights into pathogenesis, thereby providing new diagnostic capabilities and previously unexplored therapeutic targets.

Participant Inclusion Criteria:

1. Patients with Sjögren's syndrome

Participant Compensation:

Contact Information:

John Harley, MD, PhD (405)271-7766