基于通路分析的重型痤疮全基因组关联研究

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

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1056例重型痤疮患者和1056例健康对照标本，每个标本检测900015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TMPRSSllE、DDB2、RICl、CLLUlOS、IL3、PLA2G4B、SLCl6A14、SOXl7、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。

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 ache 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 ache. Results Twelve genes were identified to be associated with severe acne （P 〈 O.OO1 ）, including TMPRSS11E, DDB2, RIC1, CLLUIOS, IL3, PLA2G4B, SLC16A14, SOX17, FAHD2A, ENTPDT, MRPL50 and TXLNB. Pathway analysis revealed 5 pathways associated with severe aene （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.