Schizophrenia genetics not linked to neuropsychiatric features in childhood-onset SLE

No apparent association exists between neuropsychiatric systemic lupus erythematosus (NPSLE) and known risk loci for schizophrenia in a multiethnic cohort of patients with childhood-onset (c)SLE, reveals a recent study.

Patients from the Lupus Clinic at the Hospital for Sick Children in Toronto, Canada, were identified and included if they met at least four of the American College of Rheumatology and/or SLE International Collaborating Clinics SLE classification criteria. Eligible participants were then genotyped using the Illumina Multi-Ethnic Global Array or the Global Screening Array.

The authors then imputed ungenotyped single-nucleotide polymorphisms (SNPs) and genetically inferred ancestry. They calculated two additive schizophrenia-weighted polygenic risk scores (PRS) using genome-wide significant SNPs (p<5x10^-8) and an expanded list of SNPs with significance (p<0.05).

Two outcomes were defined in comparison to the absence of NPSLE features, namely (1) any NPSLE feature and (2) subtypes of NPSLE features (ie, psychosis and nonpsychosis NPSLE).

Finally, the authors completed logistic and multinomial regression, adjusted first for inferred ancestry only and then added for variables significantly associated with NPSLE in the cohort (p<0.05).

A total of 513 patients with cSLE (median age 13.8 years, 83 percent female, and 31 percent of European ancestry) were included in the analysis.

In ancestry-adjusted models, an increasing schizophrenia genome-wide association PRS did not correlate with NPSLE (odds ratio [OR], 1.04, 95 percent confidence interval [CI], 0.87‒1.26; p=0.62) nor with the NPSLE subtypes, psychosis (OR, 0.97, 95 percent CI, 0.73‒1.29; p=0.84) and other nonpsychosis NPSLE (OR, 1.08, 95 percent CI, 0.88‒1.34; p=0.45).

These results were consistent with those in the model including covariates (ie, ancestry, malar rash, oral/nasal ulcers, arthritis, lymphopaenia, Coombs-positive haemolytic anaemia, lupus anticoagulant, and anticardiolipin antibodies) and in the expanded PRS estimates.

“We did not observe an association between known risk loci for schizophrenia and NPSLE in a multiethnic cSLE cohort,” the authors said. “This work warrants further validation.”