
Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. This study aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Patients with SLE and high wGRS tended to have an earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict a high risk for lupus nephritis and a diverse clinical course in SLE patients.
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