Lupus & antiphospholipid syndrome
Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus
Authors' conclusion
Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes.
Study context
- Population
- Korean patients with systemic lupus erythematosus (SLE)1,243 discovery, 412 replication
- Participants
- 1,655 patients
- Comparison
- Highest vs lowest weighted genetic risk score quartile
- Outcome
- Associations between individual wGRS (112 non-HLA SNPs and HLA haplotypes) and clinical SLE subphenotypes and autoantibodies
Methodological detailsdiscovery and replication sets, customized genome-wide single-nucleotide polymorphism (SNP) array (KoreanChip), multivariable linear or logistic regression adjusted by onset age, sex, and disease duration
- Discovery and replication sets
- Customized genome-wide SNP array (KoreanChip)
- Multivariable linear or logistic regression adjusted by onset age, sex, and disease duration
Main finding
As reported in the abstract
Hazard ratio (renal disorder)
1.74
P = 2.2 × 10-8
Highest weighted genetic risk score (wGRS) quartile
Hazard ratio (anti-Sm antibody production)
1.85
P = 2.8 × 10-5
Highest wGRS quartile
- Childhood-onset SLE (<16 years) conferred the highest genetic risk vs adult-onset (16-50 years) or late-onset (>50 years) SLE
- P = 6.8 × 10-6
- wGRS correlated positively with more clinical ACR criteria (β)
- 0.143, P = 1.8 × 10-6
Further findings
| Outcome | HR | P value |
|---|---|---|
| LN class III or IV | 1.98 | P = 1.6 × 10-5 |
| LN class V | 2.79 | P = 1.0 × 10-3 |
LN class V in anti-Sm-positive SLE
- AUC
- 0.68, P = 1.8 × 10-4
Original publication
Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus. Arthritis Rheumatol. Published 11 June 2023. doi:10.
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