JAZF1 – Systemic Lupus Erythematosus Susceptibility Locus

Genome-wide association studies have implicated common variants at the JAZF1 locus in systemic lupus erythematosus (SLE). In a replication of 2,466 SNPs in 1,963 SLE cases and 4,329 controls, JAZF1 variants reached genome-wide significance with an odds ratio of 1.20 (P<5×10⁻⁸) (PMID:19838195). A subsequent pan-meta-analysis incorporating 6,835 SSc and SLE cases confirmed shared JAZF1 susceptibility for SLE with OR 1.13 (P=1.11×10⁻⁸) (PMID:23740937).

No rare coding mutations or familial segregation studies have been reported for JAZF1 in SLE, and functional assays directly linking JAZF1 variants to immune dysregulation in SLE are lacking. The evidence thus indicates a polygenic, common-variant mechanism with modest effect size. Additional sequencing in multiplex families and cell-based functional follow-up in immune subsets are required to clarify JAZF1’s pathogenic role. Key take-home: JAZF1 common variants provide a reproducible but modest contribution to SLE risk, supporting inclusion in polygenic risk scores.

References

• Nature Genetics • 2009 • A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. PMID:19838195
• Human Molecular Genetics • 2013 • A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci. PMID:23740937

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