Abstract: Objective　To explore the mechanism of pediatric bipolar disorder（PBD）and youth bipolar disorder，so as to provide novel thoughts for its basic research and clinic treatment.Methods　Papers published from January 2014 to July 2018 were included via PubMed from February 2018 to July 2018.The key words were “pediatric bipolar disorder sequencing” or “youth bipolar disorder sequencing”，and 32 papers in total were obtained.Data sets using whole-exome sequencing（WES）or transcriptome sequencing techniques in more than 10 patients were included.Finally，5 data sets were selected.Among them，4 WES data sets contained 175 potential PBD related risk genes，and 1 transcriptome sequencing data set contained 41 ones.All these genes were divided into whole-exome group（175）and transcriptome group（41）after de-weighting.Enrichment analysis of biological process（BP）was performed using DAVID，KEGG，Panther and WebGestalt.The enrichment pathway was calculated using KEGG and Panther databases.Results　Nine BP classifications with significant enrichment were obtained in the enrichment analysis of WES，which affected anionic transmembrane transport，chloridion transport，embryo development and cerebromedullary tube upgrowth the most，and some of them were related to adrenal development.Ten BP classifications with significant enrichment were obtained in the enrichment analysis of transcriptome sequencing，and abnormal expression of genes mainly concentrated in histone ubiquitination，synthesis and release of thyroxin，protein folding，and histone modification.The KEGG database stated that the main pathway with significant enrichment of whole-exome group genes were inositol phosphate metabolism and phosphatidyl inositol signal system，and of transcriptome group genes was ubiquitination-regulated protein hydrolysis.The Panther database declared that the main pathway with significant enrichment of whole-exome group genes were angiogenesis-related and Parkinson's disease-related pathways，and of transcriptome group genes could not be found clearly.Conclusion　The gene mutation of PLCD3，DAG1，APLNR，EPAS1 in patients with PBD was associated with embryo development，which is a embryonal system mutation inheriting from parents.The abnormal gene mutation or expression was related to phosphatidyl inositol signal system and angiogenesis.

Key words: Bipolar disorder, Child, Adolescent, Genomics, Gene order, Computational biology

摘要： 目的　揭示儿童青少年双相情感障碍（PBD）的发病机制，为PBD的基础研究和临床治疗提供新思路。方法　2018年2—7月，分别以“pediatric bipolar disorder sequencing”“youth bipolar disorder sequencing”为关键词，在PubMed检索2014年1月—2018年7月的文献，共获得32篇文献。挑选其中应用全外显子组测序或转录组测序研究且纳入患者例数超过10例的数据集，经检索筛选共得到5套完整数据集，包含4套全外显子组测序研究（去重之后共计包含175个潜在与PBD风险相关的基因）及1套转录组测序研究（包含41个潜在与PBD风险相关的重要基因）。去重之后的基因按照不同组学方法分成两组：来自全外显子组测序的175个基因（全外显子组）与来自转录组测序的41个基因（转录组），分别使用生物信息软件DAVID、KEGG、Panther、WebGestalt进行每组基因生物学功能（BP）的富集分析，通过KEGG、Panther数据库计算其所富集的通路。结果　全外显子组基因富集分析结果显示，共得到9个显著富集的BP分类，发生重要影响功能变异基因的主要作用与阴离子跨膜转运、氯离子运输、胚胎发育、神经管发育模式相关，另有少量基因显著富集与肾上腺发育功能相关。转录组基因富集分析结果显示，共得到10个显著富集的BP分类，发生异常表达的基因主要集中在组蛋白泛素化、甲状腺素合成与水解、蛋白折叠、组蛋白修饰等蛋白合成或水解相关的功能。全外显子组基因在KEGG数据库中显著富集的通路主要为肌醇磷酸盐代谢、磷脂酰肌醇信号系统通路；转录组基因在KEGG数据库中显著富集的通路主要为泛素化调控的蛋白水解通路。全外显子组基因在Panther数据库中显著富集的通路主要包括血管生成相关通路与帕金森疾病类通路；转录组基因在Panther数据库中未见显著富集的通路。结论　PBD患者异常突变的PLCD3、DAG1、APLNR、EPAS1等基因与胚胎发育相关，且该类变异属于遗传自父母的胚系突变；PBD患者中异常突变或表达的基因与磷脂酰肌醇信号系统以及血管生成相关。

关键词: 双相情感障碍, 儿童, 青少年, 基因组学, 基因顺序, 计算生物学