Polygenic Risk and Linked Metabolic Profile in Systemic Lupus Erythematosus: Cross-Sectional Insights

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a multifactorial origin involving genetic, epigenetic, and environmental determinants as well as some risk factors. Genetic predisposition has been quantified through polygenic risk scores (PRS), which integrate the cumulative effect of multiple single nucleotide variants (SNVs) associated with disease risk. Despite extensive research on immune and inflammatory pathways in SLE, the interplay between genetic susceptibility and metabolic dysfunction remains poorly understood. This study aimed to explore associations between SLE-related PRS and metabolic, inflammatory, and clinical parameters in adults participating in the METAINFLAMACIÓN-CM project (Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain). Polygenic predisposition contributes to variability in SLE metabolic phenotype but does not independently drive most inflammatory parameters. SLE patients displayed metabolic and inflammatory alterations relevant to cardiovascular risk, highlighting the importance of comprehensive cardiometabolic assessment. Integrating PRS with metabolic profiling may support precision personalized management and improve cardiovascular risk evaluation in SLE.