Exploring genetic targets of psoriasis using genome wide association studies (GWAS) for drug repurposing.

Psoriasis is a chronic inflammatory disease causing itching in the body and pain in the joints. Currently, no permanent cure is available at a commercial level for this disease. Genome wide association studies (GWAS) provide a deeper insight that helps in better understanding this disease and further possible cure of this disease. The major goal of the present study is to identify potent genetic targets of psoriasis disease using GWAS approach and identify drugs for repurposing. The methods used include GWAS catalogue, GeneAnalytics, canSAR protein annotation tool, VarElect, Drug bank, Proteomics database, ProTox software. By exploring GWAS catalogue, 126 psoriasis associated genes (PAG) were identified. 68 genes found to be druggable were obtained from canSAR protein annotation tool. Localization results depict that maximum genes are present in cytoplasmic cellular components. The superpathways obtained from GeneAnalytics resulted in involvement of these genes in the immune system, Jak/Stat pathway, Th17 and Wnt pathways. Two genes Interleukin 13 (IL13) and POLI are Food and Drug Administration (FDA) approved targets. Small compounds for these targets were analysed for drug-likeliness, toxicity and mutagenecity properties. The FDA approved drug pandel was found to possess desirable properties. The medications used for psoriasis causes mild to severe side effects and does not work well always. Hence we propose drug repurposing strategy to use existing drugs for new therapies. Therefore, the drug pandel could be explored further and repurposed to treat psoriasis. © King Abdulaziz City for Science and Technology 2020.