Dissecting the Causal Links Between Acne Vulgaris and Cardiometabolic Health Using Mendelian Randomization

ABSTRACT 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 genome-wide association study (GWAS) summary statistics, we assessed genetic correlations and causal relationships between acne and cardiometabolic traits via linkage disequilibrium score regression (LDSC) and bidirectional Mendelian Randomization (MR). Significant inverse genetic correlations were observed between acne and body mass index (BMI; genetic correlation estimate [rG]= -0.117, P=1.14×10⁻⁶), body fat percentage (BFP; rG=-0.156, P=4.84×10⁻¹⁰), metabolic syndrome (MetS; 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 HDL cholesterol (rG= 0.069, P=1.50×10⁻³). MR analyses supported causal effects of higher BMI (inverse-variance weighted estimate [IVW] β= -0.230, P=9.41×10⁻¹¹), BFP (IVW β = -0.052, P=1.41×10⁻¹⁰), and MetS (IVW β= -0.214, P=1.58×10⁻⁶) on lower acne risk. Multivariable MR demonstrated that MetS risk remained associated with reduced acne susceptibility after adjustment for either BMI (β= -0.31, P=5.4×10⁻¹⁰) or BFP (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 BMI, BFP and MetS risk on acne development.