Genetic variants have long been suspected to be important in psoriasis. Recent work has suggested that HLA-Cw6 on chromosome 6 is the risk variant in the PSORS1 [MIM 177900] susceptibility locus that confers the greatest risk for early onset of psoriasis. Although numerous minor susceptibility loci have been identified by linkage analysis, few biologically relevant candidates have been discovered within these intervals. Recent large-scale genome-wide association studies have yielded new candidates in genes encoding cytokines with functional relevance to psoriasis. Polymorphisms within the genes encoding the IL-12 p40 subunit, IL12B, and one of the IL-23 receptor subunits, IL23R, have been replicated in US and European populations and overlap with risk of Crohn's disease. Polymorphisms within the gene encoding IL-13, a Th2 cytokine, also confer risk for psoriasis. Variants of the gene IL15 encoding IL-15 have been identified that associate with psoriasis in a Chinese population. These discoveries pose the challenge of elucidating the role of common genetic variants in susceptibility to and manifestations of psoriasis.