Relationship between genetic risk and age of diagnosis in systemic lupus erythematosus

Canadian Network for Improved Outcomes in SLE (CaNIOS) and APPLE Investigators

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17 Citations (Scopus)


Objective. Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis. Methods. Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population. Results. The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r2 = 0.175 for GRWS; P = 0.008 and r2 = 0.178 for GRSCS; P = 0.002 and r2 = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r2 = 0.176 for GRCS; P = 0.022 and r2 = 0.176 for GRWS; P = 0.022 and r2 = 0.176 for GRSCS; P = 0.011 and r2 = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis). Conclusion. Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

Original languageEnglish
Pages (from-to)852-858
Number of pages7
JournalJournal of Rheumatology
Issue number6
Publication statusPublished - 1 Jun 2021

Bibliographical note

Funding Information:
This work was funded by a grant from the Alliance for Lupus Research (number 417516) to EDS. JBH was supported by grants from the National Institutes of Health: AI024717 (R01), AI130830 (U01), and AI148276 (R01). 1D. Dominguez, MSc, Division of Rheumatology, Hospital for Sick Children, Hospital for Sick Children, Research Institute, University of Toronto, Toronto, Ontario, Canada; 2S. Kamphuis, MD, PhD, Division of Rheumatology Department of Pediatrics, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, the Netherlands; 3J. Beyene, PhD, Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton; 4J. Wither, MD, PhD, Division of Genetics and Development, Krembil Research Institute, Arthritis Centre of Excellence, Division of Rheumatology, Toronto Western Hospital, University Health Network, Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada; 5J.B. Harley, MD, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, and US Department of Veterans Affairs Medical Center, Cincinnati, Ohio; 6I. Blanco, MD, C. Vila-Inda, MD, Albert Einstein College of Medicine, Division of Rheumatology, Bronx, New York; 7H. Brunner, MD, MSc, Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 8M. Klein-Gitleman, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 9D. McCurdy, MD,

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