Tu98 - Development of a Classification Criteria-based Polygenic Risk Score for Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by a heterogenous clinical phenotype that may present differently over time and between patients, which can create challenges for identifying cohorts of patients with SLE. The Systemic Lupus International Coordinating Clinics (SLICC) classification criteria characterize the myriad of manifestations and laboratory tests that collectively define SLE. Previously published algorithms for the identification of SLICC attributes and SLE International Classification of Disease (ICD) instances were adapted to the Electronic Medical Records and Genomics (eMERGE) Network, which combines biorepository and electronic health record data at multiple health centers across the US. Cases were defined by satisfying of four or more SLICC attributes or both a positive antinuclear body and renal SLICC attribute. A cohort of cases and controls were identified within eMERGE and stratified into African (n = 4,152) and European ancestry (n = 33,036) groups. A genome-wide association study utilizing the criteria-based case definition was conducted for each ancestry group and summary statistics from each were used to calculate the best fit polygenic risk scores (PRS). PRS for patients with ≥3 ICD SLE instances at least 30 days apart  were significantly higher than patients with < 3 SLE ICD instances in both European Americans (4.19e-4 versus -9.54e-5, p=3.24e-245) and African Americans (4.16e-3 versus 1.12e-3, p=1.44e-138). The results suggest that a rule-based algorithm consisting of individual disease components can be successfully utilized as a case definition for population genetics studies.