Researchers investigated how schizophrenia genetic susceptibility loci are associated with neuropsychiatric systemic lupus erythematosus (NPSLE) features in childhood-onset SLE (cSLE) participants.

• From the Lupus Clinic at the Hospital for Sick Children, Toronto, researchers retrieved study participants meeting ≥ 4 of the American College of Rheumatology and/or SLE International Collaborating Clinics SLE classification criteria and used the Illumina Multi-Ethnic Global Array or the Global Screening Array to genotype them.

• Imputation of ungenotyped single-nucleotide polymorphisms (SNPs) was done, and genetic inference of ancestry was performed.

• Two additive schizophrenia-weighted polygenic risk scores (PRS) were determined using genome-wide significant SNPs (P < 5 × 10^–8), and an expanded list of SNPs with significance at <em>P</em> < 0.05.

• A total of 513 participants with cSLE were included (median age at diagnosis: 13.8 years (IQR 11.2–15.6); 83% females; and 31% with European ancestry).

• In ancestry-adjusted models, there appeared no association of an increasing schizophrenia genome-wide association PRS with NPSLE, or with the NPSLE subtypes, psychosis and other nonpsychosis NPSLE.

• 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, similar results were recorded.

• Overall findings from this multiethnic cSLE cohort suggest no association between known risk loci for schizophrenia and NPSLE.