银屑病易复发、难根治，严重影响患者身心健康。申请人从事银屑病发病机制研究十年，在青年基金资助下，从基因分型、基因表达、通路分析等多角度证实LNPEP可能参与MHC I类分子抗原提呈或NF-κB信号通路影响疾病发生。收集20对患者皮损/非皮损组织及20例对照组织开展全基因组表达谱预实验，发现LNPEP在组织中表达与银屑病显著相关（P=3×10-15）。本课题基于前期疾病全基因组基因分型、全外显子测序及组织基因表达谱数据库万余例数据，拟以千人基因组数据为参考，采用Impute2软件，对LNPEP所在5q15区域行基因填补（Imputation），筛选关键基因；开展基因测序搜寻功能性致病变异；并在大样本人群中验证（5000- 5000），建立基因间生物学交互作用网络，从基因共表达研究功能学角度加以验证，并构建多基因风险预测模型，力求将基础理论成果应用于转化医学，为疾病诊断治疗靶标筛查提供突破口。

Psoriasis is a common relapsing and remitting skin disease, which severely affected physical and mental health of patients. The applicant has been working on the research of the pathogenesis of psoriasis for 10 years. Under the support of Young Scientist's Fund, we identified that the LNPEP gene may be involved in MHC class I molecules antigen presenting or the NF-κB signaling pathway for psoriasis by several different ways, such as gene genotyping, gene expression, path analysis and so on. Then we collected 20 pairs of lesions and non-lesions in each patient and 20 skin tissues of the controls to perform the whole genome expression analysis, and found that the expression of LNPEP in skins was significantly associated with psoriasis（P=3×10-15）. Based on three databases of genome-wide genotyping, exome sequencing and whole genome expression profiling, with more than ten thousand data information, This study plans to take 1000 Genomes data for reference, carry out imputation in 5q15 that LNPEP was located for the key susceptibility genes using IMPUTE2 software, search for the functional variants by conducting gene sequencing with replication in a large number of samples (5000 cases and 5000 controls), establish gene-gene biological interaction network verified by gene co-expression analysis, and then build the genetic risk prediction model, which will help to apply basic theory achievement to translational medicine, and also will be a valuable breakthrough of the target identification for the disease diagnosis and treatment in the future.