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He B, Shi J, Wang X, et al. Genome-wide pQTL analysis of protein expression regulatory networks in the human liver. BMC Biol. 2020;18(1):97doi: 10.1186/s12915-020-00830-3.
He, B., Shi, J., Wang, X., Jiang, H., & Zhu, H. J. (2020). Genome-wide pQTL analysis of protein expression regulatory networks in the human liver. BMC biology, 18(1), 97. https://doi.org/10.1186/s12915-020-00830-3
He, Bing, et al. "Genome-wide pQTL analysis of protein expression regulatory networks in the human liver." BMC biology vol. 18,1 (2020): 97. doi: https://doi.org/10.1186/s12915-020-00830-3
He B, Shi J, Wang X, Jiang H, Zhu HJ. Genome-wide pQTL analysis of protein expression regulatory networks in the human liver. BMC Biol. 2020 Aug 10;18(1):97. doi: 10.1186/s12915-020-00830-3. PMID: 32778093; PMCID: PMC7418398.
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BMC Biol. 2020 Aug 10;18(1):97. doi: 10.1186/s12915-020-00830-3.

Genome-wide pQTL analysis of protein expression regulatory networks in the human liver.

BMC biology

Bing He, Jian Shi, Xinwen Wang, Hui Jiang, Hao-Jie Zhu

Affiliations

  1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Room 4565 NUB, Ann Arbor, MI, 48109-1065, USA.
  2. Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
  3. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church Street, Room 4565 NUB, Ann Arbor, MI, 48109-1065, USA. [email protected].

PMID: 32778093 PMCID: PMC7418398 DOI: 10.1186/s12915-020-00830-3

Abstract

BACKGROUND: Previous expression quantitative trait loci (eQTL) studies have identified thousands of genetic variants to be associated with gene expression at the mRNA level in the human liver. However, protein expression often correlates poorly with mRNA levels. Thus, protein quantitative trait loci (pQTL) study is required to identify genetic variants that regulate protein expression in human livers.

RESULTS: We conducted a genome-wide pQTL study in 287 normal human liver samples and identified 900 local pQTL variants and 4026 distant pQTL variants. We further discovered 53 genome hotspots of pQTL variants. Transcriptional region mapping analysis showed that 1133 pQTL variants are in transcriptional regulatory regions. Genomic region enrichment analysis of the identified pQTL variants revealed 804 potential regulatory interactions among 595 predicted regulators (e.g., non-coding RNAs) and 394 proteins. Moreover, pQTL variants and trait-variant integration analysis implied several novel mechanisms underlying the relationships between protein expression and liver diseases, such as alcohol dependence. Notably, over 2000 of the identified pQTL variants have not been reported in previous eQTL studies, suggesting extensive involvement of genetic polymorphisms in post-transcriptional regulation of protein expression in human livers.

CONCLUSIONS: We have partially established protein expression regulation networks in human livers and generated a wealth of pQTL data that could serve as a valuable resource for the scientific community.

Keywords: Protein expression regulation; Protein quantitative trait loci; Protein-disease interaction; Proteomics

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