Genome-wide association studies (GWAS) have reproducibly associated ~40 common variants with the risk of psoriasis.However, the missing heritability is evident, in which the contributions of coding variants have not yet systematically evaluated Here we present the first large-scale whole exome analysis of coding variants for psoriasis using 42,760 Han Chinese samples by a three-stage case-control design.We discovered 15 coding variants underlying the mechanism of psoriasis, encompassing fourteen within MTHFR, NPPA, ZNF683, AIM2, C1orf141, C1orf68, KPRP, CASR, ZFYVE16, CCDC129, ZNF143, SYNE2, IFNGR2 and TMC6, one within known susceptibility gene IFIH1.Of them, thirteen genes were significantly differently expressed in skin between patients and controls.