RT Journal Article
SR Electronic
T1 Relationship between Genetic Risk and Age of Diagnosis of Systemic Lupus Erythematosus
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.200002
DO 10.3899/jrheum.200002
A1 Daniela Dominguez
A1 Sylvia Kamphuis
A1 Joseph Beyene
A1 Joan Wither
A1 John B.  Harley
A1 Irene Blanco
A1 Catarina Vila-Inda
A1 Hermine Brunner
A1 Marissa Klein-Gitleman
A1 Deborah McCurdy
A1 Dawn M.  Wahezi
A1 Thomas Lehman
A1 Marija Jelusic
YR 2020
UL http://www.jrheum.org/content/early/2020/10/13/jrheum.200002.abstract
AB Objective Specific risk alleles for childhood-onset SLE (cSLE) versus adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if: 1) There is an association between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis; and if 2) There is an association between HLA-related genetic risk score and age of SLE diagnosis. Methods Genomic DNA was obtained from 2,001 multi-ethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS) and standardized counting (GRSCS) and standardized weighted (GRSWS) scores were calculated based on independent SNPs from validated SLE-loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population. Results The analysed cohort consisted of 1,540 patients: 1,351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations with 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 for all non-HLA genetic risk scores (higher GRS the lower the age of diagnosis.) All HLA genetic risk scores 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 genetic scores correlated with higher age of diagnosis. Conclusion Our data suggested that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA genetic risk scores are associated with age of diagnosis in opposite directions.