A genome-wide integrative study of microRNAs in human liver

BMC Genomics

Research Article

Rongrong Wei¹  Snezana Mirkov²  Nancy J Cox²  R Stephanie Huang²  Eric R Gamazon²  Mark J Ratain²  Jacqueline Ramírez²  Federico Innocenti³  Wanqing Liu⁴  Min Zhang⁵  Libo Wang⁵ 

[1] Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 47907, West Lafayette, IN, USA;Department of Medicine, The University of Chicago, IL60637, Chicago, USA;Department of Medicine, The University of Chicago, IL60637, Chicago, USA;Current affiliation: Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, 27599, Chapel Hill, NC, USA;Department of Medicine, The University of Chicago, IL60637, Chicago, USA;Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 47907, West Lafayette, IN, USA;Department of Statistics, Purdue University, 47907, West Lafayette, IN, USA;

关键词: microRNA;    eQTL;    Transcriptome;    Genome-wide;    SNP;    Human liver;    Pharmacogenetics;   

DOI  :  10.1186/1471-2164-14-395

 received in 2012-09-27, accepted in 2013-05-16,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundRecent studies have illuminated the diversity of roles for microRNAs in cellular, developmental, and pathophysiological processes. The study of microRNAs in human liver tissue promises to clarify the therapeutic and diagnostic value of this important regulatory mechanism of gene expression.ResultsWe conducted genome-wide profiling of microRNA expression in liver and performed an integrative analysis with previously collected genotype and transcriptome data. We report here that the Very Important Pharmacogenes (VIP Genes), comprising of genes of particular relevance for pharmacogenomics, are under substantial microRNA regulatory effect in the liver. We set out to elucidate the genetic basis of microRNA expression variation in liver and mapped microRNA expression to genomic loci as microRNA expression quantitative trait loci (miR-eQTLs). We identified common variants that attain genome-wide significant association (p < 10-10) with microRNA expression. We also found that the miR-eQTLs are significantly more likely to predict mRNA levels at a range of p-value thresholds than a random set of allele frequency matched SNPs, showing the functional effect of these loci on the transcriptome. Finally, we show that a large number of miR-eQTLs overlap with SNPs reproducibly associated with complex traits from the NHGRI repository of published genome-wide association studies as well as variants from a comprehensive catalog of manually curated pharmacogenetic associations.ConclusionOur study provides important insights into the genomic architecture of gene regulation in a vital human organ, with important implications for our understanding of disease pathogenesis, therapeutic outcome, and other complex human phenotypes.

【 授权许可】

Unknown   
© Gamazon et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.