Abstract
Objective We examined the association between schizophrenia genetic susceptibility loci and neuropsychiatric systemic lupus erythematosus (NPSLE) features in childhood-onset SLE (cSLE) participants.
Methods Study participants from the Lupus Clinic at the Hospital for Sick Children, Toronto, met ≥4 of the ACR and/or SLICC SLE classification criteria and were genotyped using the Illumina MEGA or GSA arrays. Ungenotyped SNPs were imputed, and ancestry was genetically inferred. We calculated two additive schizophrenia weighted polygenic risk scores (PRSs) using: 1) genome-wide significant SNPs (P<5×10-8) and 2) expanded list of SNPs with significance P<0.05. We defined two outcomes compared to absence of NPSLE features: 1) any NPSLE feature and 2) subtypes of NPSLE features: psychosis and non-psychosis NPSLE. We completed logistic and multinomial regressions, first adjusted for inferred ancestry only and second including variables significantly associated with NPSLE in our cohort (P<0.05).
Results We included 513 participants with cSLE. Median age at diagnosis was 13.8 years (IQR, 11.2-15.6), 83% were female, and 31% were of European ancestry. An increasing schizophrenia GWAS PRS was not significantly associated with NPSLE (OR=1.04, [95%CI 0.87,1.26];P=0.62), nor with NPSLE subtypes: psychosis (OR=0.97, [95%CI 0.73,1.29];P=0.84) and other non-psychosis NPSLE (OR=1.08, [95%CI 0.88,1.34];v=0.44) in ancestry adjusted models. Results were similar for the model including covariates (ancestry, malar rash, oral/nasal ulcers, arthritis, lymphopenia, Coombs-positive hemolytic anemia, lupus anticoagulant and anticardiolipin antibodies), and for the expanded PRS estimates.
Conclusion We did not observe an association between known risk loci for schizophrenia and NPSLE in a multiethnic cSLE cohort. This work warrants further validation.
