Enriched pathways for major depressive disorder identified from a genome-wide association study
Enriched pathways for major depressive disorder identified from a genome-wide association study
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DOI：
10.1017/s1461145711001891
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发表时间：
2012-11-01
影响因子：
4.8
通讯作者：
Kuo, Po-Hsiu
中科院分区：
文献类型：
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作者：
Kao, Chung-Feng;Jia, Peilin;Kuo, Po-Hsiu
重度抑郁症（MDD）在世界范围内造成了严重的疾病负担，具有中等遗传性。尽管进行了大量的关联研究和现在的全基因组关联（GWA）研究，但确定重度抑郁症易感位点的成功仍然有限，这部分归因于抑郁症发病机制的复杂性。一种基于途径的分析策略，用于研究特定生物途径中各种基因的联合效应，已成为研究复杂性状的有力工具。本研究旨在利用GWA数据集识别抑郁症的丰富通路。对于每个基因，我们分别使用组合p值和最小p值估计其基因相关p值。使用来自京都基因与基因组百科全书（KEGG）和BioCarta的规范路径。我们采用了四种基于通路的分析方法（基因集富集分析、超几何检验、平方和统计、和统计）。我们使用Benjamini & Hochberg的方法对多重测试进行调整，以报告重要的通路。我们发现了17条显著富集的抑郁通路，它们呈现出低到中等程度的串扰。排名前四的途径是长期抑郁(p
Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p