%0 Journal Article %A Daniela Dominguez %A Sylvia Kamphuis %A Joseph Beyene %A Joan Wither %A John B. Harley %A Irene Blanco %A Catarina Vila-Inda %A Hermine Brunner %A Marissa Klein-Gitleman %A Deborah McCurdy %A Dawn M. Wahezi %A Thomas Lehman %A Marija Jelusic %T Relationship between Genetic Risk and Age of Diagnosis of Systemic Lupus Erythematosus %D 2020 %R 10.3899/jrheum.200002 %J The Journal of Rheumatology %P jrheum.200002 %X 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. %U https://www.jrheum.org/content/jrheum/early/2020/10/13/jrheum.200002.full.pdf