Background/Purpose: Genetics plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Up to 20% of those affected with SLE are diagnosed in childhood or adolescence. There is evidence for a higher burden of SLE susceptibility loci in those diagnosed in childhood compared to adulthood. This higher genetic burden in children may in part be attributable to consanguinity in prior generations. We hypothesized that higher coefficients of inbreeding are associated with younger age of SLE diagnosis and family history of SLE.

Methods: We included children diagnosed and followed for cSLE at The Hospital for Sick Children Lupus Clinic, Toronto (≥ 4/11 ACR classification criteria and/or ≥ 4/17 SLICC classification criteria) between1982-2014. Participants were genotyped on the Illumina Immunochip. Standard quality control methods were performed including sex inconsistency and filtering low call rates (<95%). We completed principal components (PC) analyses seeding our population with the 1000 genomes project data, to generate PCs, remove outliers and to define ancestral groups (European, African, East Asian, South Asian). Inbreeding coefficients were calculated for each child (FSuite), stratified by ancestral group. We tested the association between inbreeding coefficients and age of SLE diagnosis using linear regression models, and with family history of SLE using logistic models.

Results: Of the 389 subjects, 8 failed QC, and 23 outliers were removed from PC analyses. A total of 358 cSLE contributed to analyses. The median age of diagnosis was 13.4 (IQR10.9 – 15.1) years and the mean inbreeding coefficient was 0.05% (IQR 0.01% – 15.4%). One percent of cohort had an inbreeding coefficient comparable to the expected proportion for 1^st cousins (12.5%). We did not observe a statistically significant association between the inbreeding coefficient and age of diagnosis, adjusting for ancestry (beta = 0.15, SE 0.1 years, p-value = 0.12) nor with family history of SLE (OR = 0.93, 95% CI 0.77, 1.12).

Conclusion: We did not observe a significant association between inbreeding coefficients and age of SLE diagnosis nor with family history of SLE. Our inbreeding coefficients were low in our cohort, limiting our power to detect an association with age or family history. Replication and meta-analyses in independent cohorts are planned next steps for validating our findings.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/investigating-genome-wide-inbreeding-coefficients-and-age-of-diagnosis-in-a-multi-ethnic-population-of-childhood-onset-systemic-lupus-erythematosus-csle/