Genetic Risk for Schizophrenia Not Associated With Neuropsychiatric Features in Childhood-Onset SLE

Teenage girl looking out the window
Teenage girl looking out the window
Researchers studied the association between schizophrenia genetic susceptibility loci and neuropsychiatric features in childhood-onset systemic lupus erythematosus.

No association was observed between known risk loci for schizophrenia and neuropsychiatric features of childhood-onset systemic lupus erythematosus (SLE), according to study results published in The Journal of Rheumatology.

Previous large-scale studies have demonstrated possible genetic associations between schizophrenia and several autoimmune diseases, including SLE.

Researchers conducted a cohort study of patients with childhood-onset SLE to examine the potential relationship between genetic susceptibility to schizophrenia and neuropsychiatric SLE (NPSLE).

The cohort included patients diagnosed with childhood-onset SLE who were followed-up with between 1983 and 2018 at the Lupus Clinic of the Hospital for Sick Children in Toronto, Canada. Participants’ data were genotyped using the Illumina Multi-Ethnic Global Array or the Global Screening Array. Single-nucleotide polymorphisms (SNPs) were selected for inclusion in schizophrenia polygenic risk scores (PRSs), based on a comprehensive genome-wide association study (GWAS) conducted by the Schizophrenia Working Group of the Psychiatric Genomics Consortium. Two PRSs were computed using genome-wide significant SNPs (P <5×10-8; GWAS PRS) and an expanded list of SNPs with significance at a threshold of P <.05 (expanded PRS).

The primary study outcome was any NPSLE feature as diagnosed by pediatric rheumatologists. Outcome subtypes included psychosis and nonpsychosis NPSLE features. The association between PRSs for schizophrenia and NPSLE was tested using logistic and multinomial regression models. Models were adjusted for inferred ancestry categories and demographic and clinical variables associated with NPSLE.

The study cohort included 513 patients with childhood-onset SLE, among whom 83% were girls. Genetically inferred ancestry indicated that the majority of patients were of European (31%) or East Asian (28%) descent. Median age at diagnosis was 13.8 years. A total of 201 patients (39%) had any NPSLE feature, among whom 60 (30%) had a psychosis feature.

In ancestry-adjusted models, an increasing schizophrenia GWAS PRS was not significantly associated with NPSLE overall (odds ratio [OR], 1.04; 95% CI, 0.87-1.26; P =.62) and with the NPSLE psychosis (OR, 0.97; 95% CI, 0.73-1.29; P =.84) and nonpsychosis (OR, 1.08; 95% CI, 0.88-1.34; P =.45) subtypes. This same trend persisted in models that used the expanded PRS estimates.

The associations were also not significant after adjusting for NPSLE covariates, including malar rash, oral/nasal ulcers, arthritis, lymphopenia, Coombs-positive hemolytic anemia, lupus anticoagulant, and anticardiolipin antibodies.

Analyses of individual schizophrenia GWAS SNPs also had no significant associations with NPSLE risk.

Results from this study suggested the lack of a substantial relationship between schizophrenia PRSs and overall risk for NPSLE in patients with childhood-onset SLE.

As study limitations, the researchers noted that while the study cohort was multiethnic, the susceptibility loci for schizophrenia were derived from a primarily European GWAS; and that the PRSs may have excluded important non-European susceptibility loci.

“Knowledge of the genetics of NPSLE will provide a better understanding of the molecular mechanisms driving this complex disease, ultimately improving therapy and outcomes for people with SLE,” the researchers wrote.


Ulloa AC, Liao F, Carlomagno RL, et al. Schizophrenia genetics and neuropsychiatric features in childhood-onset systemic lupus erythematosus. J Rheumatol. Published online October 1, 2021. doi:10.3899/jrheum.210363