Genetic Pathways and Functional Subnetworks for the Complex Nature of Bipolar Disorder in Genome-Wide Association Study.
Genetic Pathways and Functional Subnetworks for the Complex Nature of Bipolar Disorder in Genome-Wide Association Study.
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DOI：
10.3389/fnmol.2021.772584
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发表时间：
2021
影响因子：
4.8
通讯作者：
Kao CF
中科院分区：
文献类型：
--
作者：
Kuo CY;Chen TY;Kao PH;Huang W;Cho CR;Lai YS;Yiang GT;Kao CF
双相情感障碍是一种复杂的精神病学特征，也被认为是一种高度实质性的遗传性，分布于世界各地。由于双相情感障碍（BPD）复杂的遗传结构，其易感基因位点的鉴定一直受到限制。包括全基因组关联（GWA）研究在内的关联研究越来越多的证据表明，需要改进分析策略，以确定BPD缺失的遗传力。更重要的是，许多研究表明BPD与痴呆症有很强的关联。我们进行了先进的途径分析策略，以研究生物功能途径中多位点的协同效应，并进一步证明了子网络中蛋白质之间的功能效应，以使用BPD的GWA数据集研究双极性复杂性的机制。我们允许双极易感基因座发挥作用，在基于路径的分析方法中占据更大的权重。从丰富的途径中鉴定出具有重要信息的基因，我们进一步使用MetaCore构建了蛋白质相互作用的功能特异性子网络。基因评分（即，最小p值）针对基因长度进行校正，并且使用Benjamini和Hochberg方法针对多重检验对结果进行校正。我们发现了87个富集的途径，是显着的BPD，其中36个途径的报告。它们中的大多数涉及多种代谢过程、神经系统、免疫系统、分子运输、细胞通讯和信号转导。据报道，三个重要的和功能相关的子网络与多个热点与几个基因本体过程的BPD。我们全面的路径网络框架表明，使用先验知识有望促进我们对复杂精神疾病（例如，BPD）与痴呆症的联系及临床意义的获得，沿着痴呆症的发生和进展。
Bipolar disorder is a complex psychiatric trait that is also recognized as a high substantial heritability from a worldwide distribution. The success in identifying susceptibility loci for bipolar disorder (BPD) has been limited due to its complex genetic architecture. Growing evidence from association studies including genome-wide association (GWA) studies points to the need of improved analytic strategies to pinpoint the missing heritability for BPD. More importantly, many studies indicate that BPD has a strong association with dementia. We conducted advanced pathway analytics strategies to investigate synergistic effects of multilocus within biologically functional pathways, and further demonstrated functional effects among proteins in subnetworks to examine mechanisms underlying the complex nature of bipolarity using a GWA dataset for BPD. We allowed bipolar susceptible loci to play a role that takes larger weights in pathway-based analytic approaches. Having significantly informative genes identified from enriched pathways, we further built function-specific subnetworks of protein interactions using MetaCore. The gene-wise scores (i.e., minimum p-value) were corrected for the gene-length, and the results were corrected for multiple tests using Benjamini and Hochberg’s method. We found 87 enriched pathways that are significant for BPD; of which 36 pathways were reported. Most of them are involved with several metabolic processes, neural systems, immune system, molecular transport, cellular communication, and signal transduction. Three significant and function-related subnetworks with multiple hotspots were reported to link with several Gene Ontology processes for BPD. Our comprehensive pathway-network frameworks demonstrated that the use of prior knowledge is promising to facilitate our understanding between complex psychiatric disorders (e.g., BPD) and dementia for the access to the connection and clinical implications, along with the development and progression of dementia.
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影响因子：
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作者：
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DOI：
10.1176/appi.ajp.2010.10091340
发表时间：
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期刊：
The American journal of psychiatry
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影响因子：
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DOI：
10.1590/s1980-57642012dn06040003
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2012-12-01
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影响因子：
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