Systemic lupus erythematosus (SLE) and Sjögren’s Disease (SD) are both complex autoimmune diseases that primarily affect women with manifestations that can span many organs and body systems and can result in severe organ damage and death. SLE is a top causes of death among young females, despite treatments. Risk of lymphoma, the most severe complication of SD, is 7-19 times higher among patients with SD than the general population. A prominent role for rare genetic variants (variants in <1% of population) in complex diseases is emerging. Little is known about the contribution of rare variants to SLE or SD; only small studies have investigated this. The goal of this study is to use whole exome sequencing to determine whether rare variants contribute to SLE and SD risk and clinical features. The aims are:
1) Identify whether rare genetic variants are associated with SLE development using whole exome sequencing.
2) Identify whether rare genetic variants are associated with SD development using whole exome sequencing.
3) Determine whether rare genetic variants are associated with SLE clinical features including age of onset and history of lupus nephritis.
4) Determine whether rare genetic variants are associated with SD clinical features including presence of autoantibodies and severity.
This project will take approximately three years to complete.
The high multi-system morbidity and vast heterogeneity in symptoms and disease manifestations of both SLE and SD underscores the importance of improving our understanding of its relevant biological mechanisms for future drug targets and therapies. Full characterization of the genetic contribution to SLE and SD, including rare variants and our planned comprehensive analyses, has the potential to transform our understanding of disease etiology, and may lead to more effective approaches to prevention, diagnosis, and treatment for both SLE and SD.