Genetic insights reveal potential therapeutic targets for lichen planus: a translational mendelian randomization framework

Lichen planus (LP), a chronic immune-mediated inflammatory disorder affecting skin/mucosa (global prevalence: 0.5–1%), lacks effective therapies due to undefined drug targets. We performed Mendelian randomization (MR) using cis-eQTLs (eQTLGen, n = 31,684) and GWAS data from FinnGen/UK Biobank, validated via summary-based MR, colocalization, drug prediction, and molecular docking. Eight druggable genes (IL18R1, RNASET2, SYK, etc.) showed robust associations with LP risk. PheWAS revealed pleiotropic links (e.g. ATP9B with metabolic traits), while functional enrichment implicated immune/metabolic pathways. Molecular docking prioritized compounds (e.g. phorbol 12-myristate 13-acetate) with strong target binding. This study identifies prioritized therapeutic targets for LP, offering a multi-omics framework to enhance drug efficacy and reduce development risks, advancing precision therapy for refractory cases.