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Identification of expression quantitative trait loci (eQTLs) in human peripheral blood mononuclear cells (PBMCs) and shared with liver and brain
Author(s) -
He Pei,
Xia Wei,
Wang Lan,
Wu Jian,
Guo YuFan,
Zeng KeQin,
Wang MingJun,
Bing PengFei,
Xie FangFei,
Lu Xin,
Zhang YongHong,
Lei ShuFeng,
Deng FeiYan
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26325
Subject(s) - expression quantitative trait loci , biology , transcriptome , peripheral blood mononuclear cell , gene , genome wide association study , genetics , single nucleotide polymorphism , gene expression , computational biology , in vitro , genotype
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.