AbstractBackground/aimsPsoriasis is a chronic immune‐mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene‐gene interactions are important genetic models for common diseases. In this study, we explore pair‐wise interactions among SNPs contributing to psoriasis susceptibility.MethodsWe first performed gene interactions with exome‐sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non‐HLA regions.ResultsWe found interactions between HLA regions were significant. We observed significant interactions between HLA‐C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10−20, OR = 0.22) and between HLA‐C*06:02 and HLA‐B:AA67 (p = 1.22 × 10−12, OR = 0.45).ConclusionThis study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant.