Genetics of Childhood‐Onset Systemic Lupus Erythematosus
Bibliographic record
Abstract
Objective Genome‐wide association studies (GWAS) have identified >100 loci for systemic lupus erythematosus (SLE). These loci may also affect age at diagnosis. We aimed to identify genetic variants for age at SLE diagnosis and to complete a GWAS of childhood‐onset SLE (cSLE) in children diagnosed <18 years of age. Methods Patients met American College of Rheumatology and/or Systemic Lupus Erythematosus International Collaborative Clinics classification criteria, had documented age at diagnosis, and were genotyped on multiethnic arrays. Ungenotyped single nucleotide polymorphisms (SNPs) and HLA alleles were imputed to multiethnic referents. Ancestry was genetically inferred. We tested known SLE loci (142 non‐HLA, 166 HLA) with log‐transformed age of SLE diagnosis, adjusted for sex and five principal components (significance threshold P < 1.6 × 10 −4 ). We also completed a GWAS of 346 patients with cSLE and 4,080 children and adolescents without SLE of European and East Asian ancestry (genome‐wide significance P < 5 × 10 −8 ). Results We included 1,489 patients with SLE, 51% of patients had cSLE, 88% of patients were female, 39% of patients were of European ancestry, 19% of patients were of East Asian ancestry, and 17% of patients were of Admixed ancestry. The median age at diagnosis was 17.7 years (interquartile range 14.0–30.9). One SLE‐risk SNP, intronic to coiled‐coil domain containing 113 ( CCDC113 ) (chromosome 16), was associated with younger age at SLE diagnosis (β = −0.12, SE = 0.03, P = 6.3 × 10 −6 ) and with cSLE versus adult‐onset SLE (aSLE). GWAS of cSLE compared to controls without SLE identified significant chromosome 6 SNP rs9268469, intronic to TSBP1‐AS1 (odds ratio 2.04 [95% confidence interval 1.59–2.63], P = 1.79 × 10 −8 ) and HLA‐DQA1 . Conclusion We identified a significant locus for younger age at SLE diagnosis, intronic to CCDC113 , among a large multiancestral cohort of children and adults with SLE. In the first GWAS of cSLE, we identified a TSBP1‐AS1 locus and an HLA‐DQA1 previously identified for aSLE.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".