Dissecting the causal links between acne vulgaris and cardiometabolic health using Mendelian randomization

Acne vulgaris, a chronic inflammatory skin condition affecting up to 85% of adolescents, has been linked to cardiometabolic traits, though causality remains unclear. Using large-scale GWAS summary statistics, we assessed genetic correlations and causal relationships between acne and cardiometabolic traits via linkage disequilibrium score regression and bidirectional Mendelian randomization. Significant inverse genetic correlations were observed between acne and body mass index (genetic correlation estimate [rG] = -0.117, P = 1.14 ×10^-6), body fat percentage (rG = -0.156, P = 4.84 × 10^-10), metabolic syndrome (rG = -0.140, P = 5.48 ×10^-11), type 2 diabetes (rG = -0.124, P = 1.00 × 10^-4), and triglycerides (rG = -0.137, P = 1.19 × 10^-6), and a positive correlation with high-density lipoprotein cholesterol (rG = 0.069, P = 1.50 × 10^-3). Mendelian randomization analyses supported causal effects of higher body mass index (inverse-variance weighted estimate β = -0.230, P = 9.41 × 10^-11), body fat percentage (variance weighted estimate β = -0.052, P = 1.41 × 10^-10), and metabolic syndrome (variance weighted estimate β = -0.214, P = 1.58 × 10^-6) on lower acne risk. Multivariable Mendelian randomization demonstrated that metabolic syndrome risk remained associated with reduced acne susceptibility after adjustment for either body mass index (β = -0.31, P = 5.4 × 10^-10) or body fat percentage (β = -0.25, P = 9.02 × 10^-6). No evidence supported acne causing any of the cardiometabolic traits. These findings suggest shared genetic architecture and support a causal role of lower body mass index, body fat percentage, and metabolic syndrome risk on acne development.