Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, P. R. China.
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu, P. R. China.
J Cell Biochem. 2018 Feb;119(2):1659-1669. doi: 10.1002/jcb.26325. Epub 2017 Sep 11.
PBMCs are essential for immunity and involved in various diseases. To identify genetic variations contributing to PBMCs transcriptome-wide gene expression, we performed a genome-wide eQTL analysis by using genome-wide SNPs data and transcriptome-wide mRNA expression data. To assess whether there are common regulation patterns shared among different tissues/organs, public datasets were utilized to identify common eQTLs shared with PBMCs in lymphoblastoid, monocytes, liver, and brain. Allelic expression imbalance (AEI) assay was employed to validate representative eQTLs identified. We identified 443 cis- and 2386 trans-eSNPs (FDR <0.05), which regulated 128 and 635 target genes, respectively. A transcriptome-wide expression regulation network was constructed, highlighting the importance of 28 pleiotropic eSNPs and 18 dually (cis- and trans-) regulated genes. Three genes, that is, TIPRL, HSPB8, and EGLN3, were commonly regulated by hundreds of eSNPs and constituted a very complex interaction network. Strikingly, the missense SNP rs371513 trans- regulated 25 target genes, which were functionally related to poly(A) RNA binding. Among 8904 eQTLs (P < 0.001) identified herein in PBMCs, a minority (163) was overlapped with lymphoblastoid, monocytes, liver, and/or brain. Besides, two cis-eSNPs in PBMC were confirmed by AEI. The present results demonstrated a comprehensive expression regulation network for human PBMCs and may provide novel insights into the pathogenesis of immunological diseases related to PBMCs.
外周血单核细胞（PBMCs）对于免疫功能至关重要，并与多种疾病相关。为了鉴定与 PBMC 转录组范围基因表达相关的遗传变异，我们使用全基因组 SNP 数据和转录组范围的 mRNA 表达数据进行了全基因组 eQTL 分析。为了评估不同组织/器官之间是否存在共同的调控模式，我们利用公共数据集鉴定了与 PBMC 共享的常见 eQTL，包括淋巴母细胞、单核细胞、肝脏和大脑。我们采用等位基因表达不平衡（AEI）检测来验证代表性的 eQTL。我们鉴定了 443 个顺式和 2386 个反式 eSNP（FDR<0.05），分别调控了 128 个和 635 个靶基因。构建了转录组范围的表达调控网络，突出了 28 个多效性 eSNP 和 18 个双重（顺式和反式）调控基因的重要性。三个基因，即 TIPRL、HSPB8 和 EGLN3，受到数百个 eSNP 的共同调控，构成了一个非常复杂的相互作用网络。引人注目的是，错义 SNP rs371513 反式调控了 25 个靶基因，这些靶基因与 poly(A) RNA 结合功能相关。在本研究中鉴定的 8904 个 PBMC 的 eQTL（P<0.001）中，只有少数（163 个）与淋巴母细胞、单核细胞、肝脏和/或大脑重叠。此外，通过 AEI 验证了 PBMC 中的两个顺式 eSNP。本研究结果展示了人类 PBMC 的全面表达调控网络，可能为与 PBMC 相关的免疫性疾病的发病机制提供新的见解。
