Genetic Variants and Polygenic Risk Scores Linked to Atopic Dermatitis Risk, Severity, and Serum <scp>IgE</scp> Levels

Atopic dermatitis (AD) is a chronic inflammatory skin disease with high heritability, yet its genetic basis, especially in non-European populations, is not fully elucidated. To identify genetic variants associated with AD and to evaluate polygenic risk scores (PRS) for predicting AD risk, severity, and serum IgE levels in a Taiwanese Han population. We conducted a genome-wide association study (GWAS) using data from the China Medical University Hospital Biobank (1031 AD cases, 2106 controls). Two PRS models were developed: PRS_AD (AD risk) and PRS_IgE (IgE levels). The cohort was split into discovery and replication sets (8:2 ratio). Logistic regression, adjusted for age, sex, and population stratification, was used. The GWAS identified a novel AD-associated locus: rs905307 in RANBP2 (OR = 0.66, p = 2.75 × 10^-8). PRS_IgE was significantly associated with increased AD risk (OR = 2.230, 95% CI = 1.815-2.741, p < 0.001) and correlated with serum IgE levels (r = 0.168, p < 0.001). Patients requiring systemic treatment for severe AD had significantly higher PRS_IgE scores (p = 0.017). This study identified a novel genetic locus associated with AD and highlights a shared genetic basis between IgE levels and AD. PRS_IgE demonstrates potential for predicting AD risk and severity, suggesting opportunities for early intervention and personalized management in the Taiwanese Han population. Further research is needed to confirm these findings and explore clinical applications.