The link between frailty and risk of psoriasis: a multimodal study integrating NHANES and Mendelian randomization

Psoriasis is a chronic, inflammatory disorder with incidence increasing markedly with age. Frailty, a multidimensional syndrome characterized by diminished physiological resilience, has emerged as a critical concern in aging populations. Despite the clinical relevance of both conditions in aging populations, the potential association between frailty and psoriasis remains poorly understood. To investigate the association between frailty and the risk of psoriasis and evaluate potential causal relationships. Cross-sectional analyses were conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. Psoriasis was defined based on self-reported physician diagnoses, while frailty was quantified using a validated 49-item frailty index. Multivariable logistic regression, subgroup analyses, and interaction tests were employed to examine associations between psoriasis and frailty. Mendelian randomization (MR) analyses were conducted utilizing genome-wide association study summary statistics. The inverse-variance weighted (IVW) method served as the primary method, supplemented by sensitivity analyses. Frailty was significantly associated with elevated psoriasis risk (OR=1.75; 95% CI: 1.31-2.33; p=0.0003). This association was amplified in adults aged ≥60 years (OR=2.17; 95% CI: 1.26-3.73) and females (OR=2.08; 95% CI: 1.48-2.91). Stratified analyses demonstrated consistency across racial/ethnic, educational, and smoking subgroups. MR analyses supported a causal effect of frailty on psoriasis (IVW-derived OR=1.13; 95% CI: 1.03-1.21; p=0.01), with sensitivity models confirming robustness. Frailty is positively associated with psoriasis risk in observational analyses, and MR analyses further support a causal relationship. These findings highlight frailty as a potential modifiable target for psoriasis prevention in aging populations.