Genetic determinants of childhood onset systemic lupus erythematosus
Authors' conclusion
These results have the potential to enhance our understanding of cSLE.
Study context
- Population
- Early-onset childhood-onset SLE (cSLE), onset prior to age 10
- Participants
- 37 participants
- Outcome
- Genetic factors of early-onset cSLE: rare, functional variants in SLE-associated genes; PRS association with age of onset and nephritis
Methodological detailswhole genome sequencing, case-only design, 153 linkage disequilibrium-independent variants analysed and compared with previously reported SLE SNPs, Rare (minor allele frequency (MAF) ≤1%), damaging (CADD≥20) variants, incl. those in monogenic SLE genes (n=49), prioritised for secondary analysis
- Whole genome sequencing, case-only design
- 153 linkage disequilibrium-independent variants analysed and compared with previously reported SLE SNPs
- Rare (MAF ≤1%), damaging (CADD≥20) variants, incl. those in monogenic SLE genes (n=49), prioritised for secondary analysis
Main finding
As reported in the abstract
Genetic determinants of early-onset cSLE
- Carried ≥1 rare, pathogenic variant in monogenic SLE genes
- 37.8%
- Rare, damaging, pathogenic variants identified, incl. mitochondrial protein degradation genes (AFG3L2, SPG7) and interferon pathway genes (IFIH1, IFNGR1)
- 31, 012
- Higher polygenic risk score (PRS) associated with increased nephritis odds
- p=0.0092
- PRS not associated with age of onset
- p>0.05
Further findings
Burden testing (SKAT-O) of rare variants (MAF≤ 5%)
- Nominal enrichment in immune-related genes, incl. ISG15, PSMB9 and RNASEH2A (type I interferon and antigen presentation pathways)
Original publication
Genetic determinants of childhood onset systemic lupus erythematosus. Lupus Sci Med. Published 23 June 2026. doi:10.
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