Objective To investigate gene pathways associated with severe acne.Methods Kyoto encyclopedia of genes and genomes (KEGG)-based pathway analysis was conducted using the genome-wide association study (GWAS) data on 1 056 patients with severe acne and 1 056 healthy controls,and each testee was tested for 900 015 SNPs.A hypergeometric distribution test was used to analyze the relationship between each pathway and severe acne,and the false discovery rate (FDR) to correct for multiple testing.Any pathway with an adjusted P value of ＜ 0.05 was considered to be associated with severe acne.Results Twelve genes were identified to be associated with severe acne (P ＜ 0.001),including TMPRSS11E,DDB2,RIC1,CLLU1OS,IL3,PLA2G4B,SLC16A14,SOX17,FAHD2A,ENTPD7,MRPL50 and TXLNB.Pathway analysis revealed 5 pathways associated with severe acne (adjusted P ＜ 0.05),including the prolactin signaling pathway,hepatitis C,renal cell carcinoma,high affinity receptor for immunoglobulin E (Fc epsilon RI) signaling pathway,and tyrosine metabolism.Conclusion The 5 identified pathways are associated with severe acne,which affect the endocrine,immune and metabolic processes in the human body.