NOTCH4 encodes a member of the Notch family that play a role in a variety of developmental processes by controlling cell fate decisions. NOTCH4 has been predominantly associated with neuropsychiatric disorders ; little information is available on the association with psoriasis. IER3, an early response gene that is induced by ionizing and ultraviolet radiation, is widely expressed in epithelial and endocrine tissues and the expression is regulated by multiple transcriptional factors such as NF-kappaB/rel, p53 and c-Myc. It accelerates cell cycle progression and supports the survival of T cells, causing autoimmune disease and the development of T cell lymphoma. OR12D2, olfactory receptors interact with odorant molecules in the nose to initiate a neuronal response that VE-822 triggers the perception of a smell. Defects in COL11A2 are the cause of deafness autosomal dominant type 13, form of sensorneural hearing loss, which results from damage to the neural receptors of the inner ear, the nerve pathways to the brain. Our study may have some important implications for searching for genetic variants associated with complex human disorders. Primary nature of psoriasis is as an epithelial and immunological disorder with autoimmune cause of inflammatory process. Genetic components of both immune system and the epidermis contribute to the disease. Previous single SNP-phenotype analysis may not reflect the nature of parthenogenesis of the disease. Multiple regression analysis allows us to examine how multiple relatively independent genes together contribute to the risk of disease. It is believed that environmental factors play a certain role in the development of psoriasis. Identification of genetic association in those environmental response genes may help to elucidate the molecular mechanism of the disease. In summary, through multiple regression analysis of SNPs in MHC loci, we found SNPs in classical HLA gene shared between two major skin disorders–psoriasis and vitiligo. In addition to classical HLA genes such as HLA-C, HLA-B and HLA-DQA2, we also find association of non-HLA genes in the MHC region such as POU5F1, NFKBIL1, NOTCH4, MICA, IER3 and OR12D2 with psoriasis. Our analysis may provide the first genetic evidence that psoriasis is involved with multiple independent components of immune response, inflammation, skin keratinization and proliferation, autoimmune and stress-related pathways. This multimarker analysis may provide a basis for the disease-prediction based on genetic variants associated with the disease.