Higher Genetic Loads Linked to Worse Systemic Lupus Save

A Korean study of a large systemic lupus erythematosus (SLE) cohort shows by genomic analysis, that higher weighted genetic risk scores (wGRS) is associated with earlier SLE onset, higher anti–Sm antibody positivity, lupus nephritis and more diverse lupus manifestations.

Genotyping of 1,655 SLE patients using a customized genome-wide single-nucleotide polymorphism (SNP) array, yielded a weighted genetic risk score (wGRS) that was correlated with clinical SLE subphenotypes and autoantibodies.

The highest genetic risk was seen with childhood-onset SLE (<16 years) compared with adult-onset (16–50 years) or late-onset (>50 years) SLE (P = 6.8 × 10−6).

High wGRS were significantly associated with SLE manifestations and the number of clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6).

wGRS was also associated with a risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10−8), especially proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3).  wGRS and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5) were significantly linked.

Genetic profiling may prove useful in predicting the risk for lupus nephritis andmore aggressive clinical SLE.