Rare Variants in Systemic Sclerosis
Abstract
Systemic sclerosis (SSc, scleroderma) is an autoimmune disease with no known cause and no cure. SSc has the highest mortality rate of all the defined autoimmune diseases (including systemic lupus erythematosus, myositis, and rheumatoid arthritis). The high mortality is due to internal organ complications that impair function of the lungs, the gastrointestinal tract, the heart, and other organs. In terms of causation, it is estimated that susceptibility to this disease can be explained, at least in part, by particular genetic variants. Although several genetic areas have been identified as being associated with the disease, no particular gene or genes are known. This limits our understanding of the disease and decreases our ability to identify the specific biological pathways that are responsible for organ damage and which could be targets for novel treatments. The overall goal of this project is to specifically identify these genetic variations, including rare ones, that increase susceptibility to SSc and that influence organ complications. Biological pathways influenced by these variations will provide insight into the mechanism of disease and provide clues to more effective treatment. The immediate outcome (short-term impact) of this project will be the identification of causal variations in multiple pathways associated with SSc susceptibility while the long-range impact will be the identification of how these gene variations cause disease. This application combines the genetic, clinical, and sample repository resources at the University of Texas - Houston (UT-H) (Principal Investigator Mayes and Co-Investigators Assassi, Pedroza, and Milewicz) with the powerful sequencing and analysis capabilities of the Baylor College of Medicine (BCM) (Partnering PI Lee and Co-Investigators Burrage and Chan). Dr. Lee is Chairman of the Department of Molecular and Human Genetics at BCM. The Baylor Human Genome Sequencing Center (HGSC) was instrumental in completion of the initial Human Genome Project in 1990s and was subsequently selected as one of only three National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)-supported sequencing centers. The interaction between investigators at UT-H and BCM is further facilitated by the close proximity of these two institutions (UT-H and BCM), which are located across the street from each other in the Texas Medical Center campus. We have forged this new partnership to overcome the current barriers to progress in SSc genetics and advance the field to the next stage of discovery. Thus, each of the PIs brings complementary skills and perspectives to the research project and will work synergistically to accomplish our aims.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810499
Entities
People
- Brendan Lee
Organizations
- Baylor College of Medicine
- United States Army