BMI matters: understanding the link between weight and severe psoriasis.

This study aims to investigate the causal relationship between Body Mass Index (BMI) and the severity of Psoriasis (PsO) using bidirectional Mendelian Randomization (MR) and regression analyses. We conducted a multicenter study which combined bidirectional MR analyses with regression analyses. The MR analyses included 366,776 individuals from the largest up-to-date published BMI Genome-Wide Association Study (GWAS) data. Regression analyses were performed on 1,979 patients with psoriasis from 12 participating centers (from October 31, 2019, to May 31, 2022). We assessed the impact of BMI on PsO severity using odds ratios (ORs) and regression coefficients for three key measures: the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI). Two independent MR analyses revealed a significant causal association between BMI and PsO development. The first MR1 analysis showed that an increased BMI is significantly associated with a higher risk of psoriasis, with odds ratios of 2.28 (95% CI 1.33-3.92; p = 0.003). A subsequent MR2 analysis yielded consistent results, presenting an odds ratio of 2.37 (95% CI 1.16-4.85; p = 0.018) using the inverse-variance weighted method. Logistic regression showed that for every 1-unit increase in BMI (unadjusted covariates), the risk of severe psoriasis (PASI ≥ 10, BSA ≥ 10%, DLQI ≥ 10) increased by 6%, 6%, and 3%, respectively. Linear regression analysis revealed that each unit increase in BMI (not standardised) was associated with an increase of 0.25 units in the mean PASI score (p < 0.001), 0.34 units in the BSA score (p = 0.001), and 0.14 units in the DLQI score (95% CI 0.05-0.23; p = 0.001). From both the genetic and clinical severity assessment perspectives, it has been verified that abnormal weight gain is correlated with the severity of the condition in psoriasis patients. Clinicians should prioritize weight management and nutritional balance in the management of psoriatic disease. Clinicaltrials.gov: ChiCTR1900024852, date of registration: 2019-07-31.