Recent human genetic studies suggest that cells of the innate immune system have a primary role in the pathogenesis of neurodegenerative diseases. However, the results from these studies often do not elucidate how the genetic variants affect the biology of these cells to modulate disease risk. Here, we applied a tensor decomposition method to uncover disease associated gene networks linked to distal genetic variation in stimulated human monocyte and macrophage gene expression profiles. We report robust evidence that some disease associated genetic variants affect the expression of multiple genes in trans. These include a Parkinson's disease locus influencing the expression of genes mediated by a protease that controls lysosomal function, and Alzheimer's disease loci influencing the expression of genes involved in type 1 interferon signaling, myeloid phagocytosis, and complement cascade pathways. Overall, we uncover gene networks in induced innate immune cells linked to disease associated genetic variants, which may help elucidate the underlying biology of disease.

中文翻译：

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受刺激的单核细胞和巨噬细胞基因表达谱的张量分解可识别神经退行性疾病特异性反式 eQTL。

最近的人类遗传学研究表明，先天免疫系统的细胞在神经退行性疾病的发病机制中起着主要作用。然而，这些研究的结果通常无法阐明遗传变异如何影响这些细胞的生物学特性以调节疾病风险。在这里，我们应用张量分解方法来揭示与受刺激的人类单核细胞和巨噬细胞基因表达谱中的远端遗传变异相关的疾病相关基因网络。我们报告了强有力的证据，表明一些与疾病相关的遗传变异影响多个反式基因的表达。其中包括影响由控制溶酶体功能的蛋白酶介导的基因表达的帕金森病位点，以及影响参与 1 型干扰素信号传导、骨髓吞噬作用和补体级联途径的基因表达的阿尔茨海默病位点。总体而言，我们发现了与疾病相关遗传变异相关的诱导先天免疫细胞中的基因网络，这可能有助于阐明疾病的潜在生物学原理。