基于通路分析的重型痤疮全基因组关联研究

目的 探讨与重型痤疮相关的基因通路。方法 使用全基因组关联研究（GWAS）的芯片数据，包括1 056例重型痤疮患者和1 056例健康对照标本，每个标本检测900 015个SNP位点。对重型痤疮进行基因通路（KEGG数据库定义）分析。采用超几何分布检验计算每条通路与重型痤疮的关系，使用错误发现率（FDR）对得到的结果进行多重检验校正，校正后P < 0.05视为通路与重型痤疮相关。结果 统计分析发现12条基因与重度痤疮相关（P < 0.001），包括TMPRSS11E、DDB2、RIC1、CLLU1OS、IL3、PLA2G4B、SLC16A14、SOX17、FAHD2A、ENTPD7、MRPL50、TXLNB。通路分析发现，5条通路与重型痤疮相关（校正后P < 0.05），包括催乳素信号通路、丙型肝炎、肾细胞癌、高亲和力IgE受体信号通路、酪氨酸代谢。结论 本研究发现5条通路与重型痤疮相关，分别涉及人体的内分泌、免疫、代谢等过程。

Pathway-based analysis of genome-wide association study data on severe acne

Yang Jiankang, Feng Jiaqi, Zhang Ping, Cao Guangqiong, He Li, Wu WenjuanSchool of Basic Medical Sciences, Dali University, Dali 671000, China （Yang JK）; Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming 650000, China （Feng JQ, He L, Wu WJ）; Center of Health Checkup, First Affiliated Hospital of Kunming Medical University, Kunming 650000, China （Cao GQ）; Clinical Laboratory, Qujing First People′s Hospital, Qujing 655000, Yunnan, China （Zhang P）Corresponding authors: He Li, Email: helikm2662@126.com; Wu Wenjuan, Email: wuwj1021@126.com 【Abstract】 Objective To investigate gene pathways associated with severe acne. Methods Kyoto encyclopedia of genes and genomes （KEGG）-based pathway analysis was conducted using the genome-wide association study （GWAS） data on 1 056 patients with severe acne and 1 056 healthy controls，and each testee was tested for 900 015 SNPs. A hypergeometric distribution test was used to analyze the relationship between each pathway and severe acne, and the false discovery rate （FDR） to correct for multiple testing. Any pathway with an adjusted P value of < 0.05 was considered to be associated with severe acne. Results Twelve genes were identified to be associated with severe acne（P < 0.001）, including TMPRSS11E, DDB2, RIC1, CLLU1OS, IL3, PLA2G4B, SLC16A14, SOX17, FAHD2A, ENTPD7, MRPL50 and TXLNB. Pathway analysis revealed 5 pathways associated with severe acne （adjusted P < 0.05）, including the prolactin signaling pathway, hepatitis C, renal cell carcinoma, high affinity receptor for immunoglobulin E （Fc epsilon RI） signaling pathway, and tyrosine metabolism. Conclusion The 5 identified pathways are associated with severe acne, which affect the endocrine, immune and metabolic processes in the human body.