LARGE-SCALE robust analyses link lupus genetic predisposition to distinct clinical manifestations across biobank and patient cohorts.
Key Finding: Genetic Risk Factors in Lupus
Genetic risk factors in lupus appear to shape specific clinical features of systemic lupus erythematosus. Using population and clinical datasets, investigators found that higher inherited susceptibility was associated with several American College of Rheumatology 1982 criteria and related manifestations. These signals suggest that genetics may help anticipate which sub-phenotypes are more likely to emerge over the disease course.
Study Design and Cohorts
Researchers first aligned public biobank records with the 11 ACR-82 classification criteria and evaluated whether elevated genetic predisposition to systemic lupus erythematosus increased the odds of relevant manifestations. The analysis leveraged a large national resource with more than 218,000 individuals and modeled the cumulative effect of 57 known risk variants. The team then validated these observations in a clinical cohort of 1,487 genotyped Scandinavian patients with detailed phenotyping. From the public datasets they built manifestation-specific genetic risk scores and tested each score against its corresponding criterion using logistic regression.
Results And Clinical Signals
In the biobank, the cumulative effect of systemic lupus erythematosus risk variants was linked to rosacea with an odds ratio of 1.09, polyarthropathies with an odds ratio of 1.10, pleural effusions with an odds ratio of 1.09, and hemolytic anemia with an odds ratio of 1.32. Within the clinical cohort, five of eleven genetic risk scores were associated with their matching ACR-82 features. Arthritis and renal disorder each showed odds ratios of 1.15. Neurologic disorder demonstrated an odds ratio of 1.24. Hematologic disorder showed an odds ratio of 1.12. The strongest association was observed for immunologic disorder with an odds ratio of 1.37. Together, these findings indicate that known risk variants contribute to at least half of the canonical criteria.
Implications For Practice
These results support a future in which genetic risk factors in lupus inform patient counseling, surveillance priorities, and research stratification by sub-phenotype. Translation to routine care will require additional validation across diverse populations and integration with serologic markers and clinical predictors. For now, the data provide mechanistic context for heterogeneity in systemic lupus erythematosus and a rationale to explore genetic risk scores as complementary tools alongside established criteria and standard monitoring.
Reference: Reid S et al. Genetic risk factors and clinical manifestations of systemic lupus erythematosus: Large-scale analysis of genetic predisposition and disease subtypes. J Intern Med. 2025. doi: 10.1111/joim.70040.
