Huan Tianxiao, Rong Jian, Liu Chunyu, Zhang Xiaoling, Tanriverdi Kahraman, Joehanes Roby, Chen Brian H, Murabito Joanne M, Yao Chen, Courchesne Paul, Munson Peter J, O'Donnell Christopher J, Cox Nancy, Johnson Andrew D, Larson Martin G, Levy Daniel, Freedman Jane E
1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20824, USA.
Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02118, USA.
Nat Commun. 2015 Mar 20;6:6601. doi: 10.1038/ncomms7601.
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. Here we present a miR-eQTL mapping study of whole blood from 5,239 individuals, and identify 5,269 cis-miR-eQTLs for 76 mature microRNAs. Forty-nine per cent of cis-miR-eQTLs are located 300-500 kb upstream of their associated intergenic microRNAs, suggesting that distal regulatory elements may affect the interindividual variability in microRNA expression levels. We find that cis-miR-eQTLs are highly enriched for cis-mRNA-eQTLs and regulatory single nucleotide polymorphisms. Among 243 cis-miR-eQTLs that were reported to be associated with complex traits in prior genome-wide association studies, many cis-miR-eQTLs miRNAs display differential expression in relation to the corresponding trait (for example, rs7115089, miR-125b-5p and high-density lipoprotein cholesterol). Our study provides a roadmap for understanding the genetic basis of miRNA expression, and sheds light on miRNA involvement in a variety of complex traits.
鉴定微小RNA表达数量性状基因座（miR - eQTL）有助于深入了解微小RNA转录的调控机制，并有助于阐明微小RNA作为复杂性状介导因子的作用。在此，我们对5239名个体的全血进行了miR - eQTL定位研究，鉴定出76种成熟微小RNA的5269个顺式miR - eQTL。49%的顺式miR - eQTL位于其相关基因间微小RNA上游300 - 500 kb处，这表明远端调控元件可能影响微小RNA表达水平的个体间差异。我们发现顺式miR - eQTL高度富集顺式mRNA - eQTL和调控单核苷酸多态性。在先前全基因组关联研究中报道的与复杂性状相关的243个顺式miR - eQTL中，许多顺式miR - eQTL的微小RNA在相应性状方面表现出差异表达（例如，rs7115089、miR - 125b - 5p与高密度脂蛋白胆固醇）。我们的研究为理解微小RNA表达的遗传基础提供了路线图，并揭示了微小RNA在多种复杂性状中的作用。
