Zhao Min, Li XiaoMo, Qu Hong
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing, 100871, China.
Sci China Life Sci. 2013 Dec;56(12):1086-96. doi: 10.1007/s11427-013-4573-2. Epub 2013 Dec 5.
Eating disorder is a group of physiological and psychological disorders affecting approximately 1% of the female population worldwide. Although the genetic epidemiology of eating disorder is becoming increasingly clear with accumulated studies, the underlying molecular mechanisms are still unclear. Recently, integration of various high-throughput data expanded the range of candidate genes and started to generate hypotheses for understanding potential pathogenesis in complex diseases. This article presents EDdb (Eating Disorder database), the first evidence-based gene resource for eating disorder. Fifty-nine experimentally validated genes from the literature in relation to eating disorder were collected as the core dataset. Another four datasets with 2824 candidate genes across 601 genome regions were expanded based on the core dataset using different criteria (e.g., protein-protein interactions, shared cytobands, and related complex diseases). Based on human protein-protein interaction data, we reconstructed a potential molecular sub-network related to eating disorder. Furthermore, with an integrative pathway enrichment analysis of genes in EDdb, we identified an extended adipocytokine signaling pathway in eating disorder. Three genes in EDdb (ADIPO (adiponectin), TNF (tumor necrosis factor) and NR3C1 (nuclear receptor subfamily 3, group C, member 1)) link the KEGG (Kyoto Encyclopedia of Genes and Genomes) "adipocytokine signaling pathway" with the BioCarta "visceral fat deposits and the metabolic syndrome" pathway to form a joint pathway. In total, the joint pathway contains 43 genes, among which 39 genes are related to eating disorder. As the first comprehensive gene resource for eating disorder, EDdb ( http://eddb.cbi.pku.edu.cn ) enables the exploration of gene-disease relationships and cross-talk mechanisms between related disorders. Through pathway statistical studies, we revealed that abnormal body weight caused by eating disorder and obesity may both be related to dysregulation of the novel joint pathway of adipocytokine signaling. In addition, this joint pathway may be the common pathway for body weight regulation in complex human diseases related to unhealthy lifestyle.
饮食失调是一组生理和心理紊乱疾病，影响着全球约1%的女性人口。尽管随着研究积累，饮食失调的遗传流行病学日益清晰，但潜在的分子机制仍不明确。最近，各种高通量数据的整合扩大了候选基因的范围，并开始为理解复杂疾病的潜在发病机制提出假设。本文介绍了EDdb（饮食失调数据库），这是首个基于证据的饮食失调基因资源。从文献中收集了59个与饮食失调相关的经实验验证的基因作为核心数据集。基于核心数据集，使用不同标准（如蛋白质-蛋白质相互作用、共享细胞带和相关复杂疾病）扩展了另外四个包含601个基因组区域中2824个候选基因的数据集。基于人类蛋白质-蛋白质相互作用数据，我们重建了一个与饮食失调相关的潜在分子子网。此外，通过对EDdb中基因的综合通路富集分析，我们在饮食失调中鉴定出一条扩展的脂肪细胞因子信号通路。EDdb中的三个基因（脂联素（ADIPO）、肿瘤坏死因子（TNF）和核受体亚家族3 C组成员1（NR3C1））将京都基因与基因组百科全书（KEGG）的“脂肪细胞因子信号通路”与BioCarta的“内脏脂肪沉积与代谢综合征”通路连接起来，形成一条联合通路。该联合通路总共包含43个基因，其中39个基因与饮食失调相关。作为首个饮食失调的综合基因资源，EDdb（http://eddb.cbi.pku.edu.cn）能够探索基因与疾病的关系以及相关疾病之间的相互作用机制。通过通路统计研究，我们发现饮食失调和肥胖导致的体重异常可能都与脂肪细胞因子信号新联合通路的失调有关。此外，这条联合通路可能是与不健康生活方式相关的复杂人类疾病中体重调节的共同通路。
