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Abstract：
Whole-genome transcription has been measured in peripheral blood samples as a candidate biomarker of inflammation associated with major depressive disorder.
We searched for all case-control studies on major depressive disorder that reported microarray or RNA sequencing measurements on whole blood or peripheral blood mononuclear cells. Primary datasets were reanalyzed, when openly accessible, to estimate case-control differences and to evaluate the functional roles of differentially expressed gene lists by technically harmonized methods.
We found 10 eligible studies (N = 1754 depressed cases and N = 1145 healthy controls). Fifty-two genes were called significant by 2 of the primary studies (published overlap list). After harmonization of analysis across 8 accessible datasets (n = 1706 cases, n = 1098 controls), 272 genes were coincidentally listed in the top 3% most differentially expressed genes in 2 or more studies of whole blood or peripheral blood mononuclear cells with concordant direction of effect (harmonized overlap list). By meta-analysis of standardized mean difference across 4 studies of whole-blood samples (n = 1567 cases, n = 954 controls), 343 genes were found with false discovery rate <5% (standardized mean difference meta-analysis list). These 3 lists intersected significantly. Genes abnormally expressed in major depressive disorder were enriched for innate immune-related functions, coded for nonrandom protein-protein interaction networks, and coexpressed in the normative transcriptome module specialized for innate immune and neutrophil functions.
Quantitative review of existing case-control data provided robust evidence for abnormal expression of gene networks important for the regulation and implementation of innate immune response. Further development of white blood cell transcriptional biomarkers for inflamed depression seems warranted.
We searched for all case-control studies on major depressive disorder that reported microarray or RNA sequencing measurements on whole blood or peripheral blood mononuclear cells. Primary datasets were reanalyzed, when openly accessible, to estimate case-control differences and to evaluate the functional roles of differentially expressed gene lists by technically harmonized methods.
We found 10 eligible studies (N = 1754 depressed cases and N = 1145 healthy controls). Fifty-two genes were called significant by 2 of the primary studies (published overlap list). After harmonization of analysis across 8 accessible datasets (n = 1706 cases, n = 1098 controls), 272 genes were coincidentally listed in the top 3% most differentially expressed genes in 2 or more studies of whole blood or peripheral blood mononuclear cells with concordant direction of effect (harmonized overlap list). By meta-analysis of standardized mean difference across 4 studies of whole-blood samples (n = 1567 cases, n = 954 controls), 343 genes were found with false discovery rate <5% (standardized mean difference meta-analysis list). These 3 lists intersected significantly. Genes abnormally expressed in major depressive disorder were enriched for innate immune-related functions, coded for nonrandom protein-protein interaction networks, and coexpressed in the normative transcriptome module specialized for innate immune and neutrophil functions.
Quantitative review of existing case-control data provided robust evidence for abnormal expression of gene networks important for the regulation and implementation of innate immune response. Further development of white blood cell transcriptional biomarkers for inflamed depression seems warranted.
摘要：
已经在外周血样品中测量了全基因组转录作为与重度抑郁症相关的炎症的候选生物标志物。
我们搜索了所有关于重度抑郁症的病例对照研究，这些研究报告了对全血或外周血单核细胞的微阵列或RNA测序测量。重新分析了原始数据集，当公开访问时，评估病例对照差异，并通过技术统一的方法评估差异表达基因列表的功能作用。
我们发现了10项符合条件的研究（N=1754例抑郁症和N=1145例健康对照）。52个基因被认为是有意义的2个主要研究（已发表的重叠列表）。在8个可访问数据集的分析统一后(n=1706例，n=1098控件)，在2个或更多个全血或外周血单核细胞的研究中，272个基因被巧合地列为前3％最差异表达的基因，具有一致的作用方向（协调重叠列表）。通过对4项全血样本研究的标准化平均差异进行荟萃分析(n=1567例，n=954个控件)，发现343个基因的错误发现率<5%(标准化平均差异荟萃分析列表)。这三个列表明显交叉。在重度抑郁症中异常表达的基因富含先天免疫相关功能，编码非随机蛋白质-蛋白质相互作用网络，并在专门用于先天免疫和中性粒细胞功能的规范转录组模块中共表达。
对现有病例对照数据的定量审查为对先天免疫应答的调节和实施重要的基因网络的异常表达提供了有力的证据。似乎有必要进一步开发炎症抑郁症的白细胞转录生物标志物。
我们搜索了所有关于重度抑郁症的病例对照研究，这些研究报告了对全血或外周血单核细胞的微阵列或RNA测序测量。重新分析了原始数据集，当公开访问时，评估病例对照差异，并通过技术统一的方法评估差异表达基因列表的功能作用。
我们发现了10项符合条件的研究（N=1754例抑郁症和N=1145例健康对照）。52个基因被认为是有意义的2个主要研究（已发表的重叠列表）。在8个可访问数据集的分析统一后(n=1706例，n=1098控件)，在2个或更多个全血或外周血单核细胞的研究中，272个基因被巧合地列为前3％最差异表达的基因，具有一致的作用方向（协调重叠列表）。通过对4项全血样本研究的标准化平均差异进行荟萃分析(n=1567例，n=954个控件)，发现343个基因的错误发现率<5%(标准化平均差异荟萃分析列表)。这三个列表明显交叉。在重度抑郁症中异常表达的基因富含先天免疫相关功能，编码非随机蛋白质-蛋白质相互作用网络，并在专门用于先天免疫和中性粒细胞功能的规范转录组模块中共表达。
对现有病例对照数据的定量审查为对先天免疫应答的调节和实施重要的基因网络的异常表达提供了有力的证据。似乎有必要进一步开发炎症抑郁症的白细胞转录生物标志物。
