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Research ArticlePediatric Rheumatology

Schizophrenia Genetics and Neuropsychiatric Features in Childhood-onset Systemic Lupus Erythematosus

Ana C. Ulloa, Fangming Liao, Raffaella L. Carlomagno, Talia Diaz, Daniela Dominguez, Deborah M. Levy, Lawrence Ng, Andrea M. Knight and Linda T. Hiraki
The Journal of Rheumatology February 2022, 49 (2) 192-196; DOI: https://doi.org/10.3899/jrheum.210363
Ana C. Ulloa
1A.C. Ulloa, MPH, Genetics & Genome Biology, Research Institute, The Hospital for Sick Children;
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Fangming Liao
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Raffaella L. Carlomagno
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Talia Diaz
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Daniela Dominguez
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Deborah M. Levy
3D.M. Levy, MD, MS, Division of Rheumatology, The Hospital for Sick Children, and Department of Pediatrics, The University of Toronto;
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Lawrence Ng
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Andrea M. Knight
2F. Liao, MSc, R.L. Carlomagno, MD, T. Diaz, MD, D. Dominguez, MD, MSc, L. Ng, BSc, A.M. Knight, MD, MSCE, Division of Rheumatology, The Hospital for Sick Children;
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Linda T. Hiraki
4L.T. Hiraki, MD, FRCPC, ScD, Genetics & Genome Biology, Research Institute, and Division of Rheumatology, The Hospital for Sick Children, and Department of Pediatrics, The University of Toronto, Toronto, Ontario, Canada.
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  • For correspondence: linda.hiraki@sickkids.ca
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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 American College of Rheumatology and/or SLE International Collaborating Clinics SLE classification criteria and were genotyped using the Illumina Multi-Ethnic Global Array or the Global Screening Array. Ungenotyped single-nucleotide polymorphisms (SNPs) were imputed, and ancestry was genetically inferred. We calculated 2 additive schizophrenia-weighted polygenic risk scores (PRS) using (1) genome-wide significant SNPs (P < 5 × 10–8), and (2) an expanded list of SNPs with significance at P < 0.05. We defined 2 outcomes compared to absence of NPSLE features: (1) any NPSLE feature, and (2) subtypes of NPSLE features (psychosis and nonpsychosis NPSLE). We completed logistic and multinomial regressions, first adjusted for inferred ancestry only and then added for 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 genome-wide association PRS was not associated with NPSLE (OR 1.04, 95% CI 0.87–1.26, P = 0.62), nor with the NPSLE subtypes, psychosis (OR 0.97, 95% CI 0.73–1.29, P = 0.84) and other nonpsychosis NPSLE (OR 1.08, 95% CI 0.88–1.34, P = 0.45), 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.

Key Indexing Terms:
  • childhood
  • genetics
  • neuropsychiatric lupus
  • rheumatology
  • schizophrenia
  • systemic lupus erythematosus
  • Accepted for publication September 23, 2021.
  • © 2022 by the Journal of Rheumatology
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Schizophrenia Genetics and Neuropsychiatric Features in Childhood-onset Systemic Lupus Erythematosus
Ana C. Ulloa, Fangming Liao, Raffaella L. Carlomagno, Talia Diaz, Daniela Dominguez, Deborah M. Levy, Lawrence Ng, Andrea M. Knight, Linda T. Hiraki
The Journal of Rheumatology Feb 2022, 49 (2) 192-196; DOI: 10.3899/jrheum.210363

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Schizophrenia Genetics and Neuropsychiatric Features in Childhood-onset Systemic Lupus Erythematosus
Ana C. Ulloa, Fangming Liao, Raffaella L. Carlomagno, Talia Diaz, Daniela Dominguez, Deborah M. Levy, Lawrence Ng, Andrea M. Knight, Linda T. Hiraki
The Journal of Rheumatology Feb 2022, 49 (2) 192-196; DOI: 10.3899/jrheum.210363
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Keywords

CHILDHOOD
GENETICS
neuropsychiatric lupus
RHEUMATOLOGY
schizophrenia
SYSTEMIC LUPUS ERYTHEMATOSUS

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Keywords

  • childhood
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  • rheumatology
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  • systemic lupus erythematosus

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