Genome-wide identification of microRNA expression quantitative trait loci.

Autor: Huan T; 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., Rong J; Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02118, USA., Liu C; 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., Zhang X; 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland 20824, USA., Tanriverdi K; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA., Joehanes R; 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 [3] Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20824, USA [4] Harvard Medical School, Harvard University, Boston, Massachusetts 02115, USA [5] Hebrew SeniorLife, Boston, Massachusetts 02131, USA., Chen BH; 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., Murabito JM; 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA., Yao C; 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., Courchesne P; 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., Munson PJ; Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20824, USA., O'Donnell CJ; 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland 20824, USA., Cox N; Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA., Johnson AD; 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland 20824, USA., Larson MG; 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02118, USA., Levy D; 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., Freedman JE; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Mar 20; Vol. 6, pp. 6601. Date of Electronic Publication: 2015 Mar 20.
DOI: 10.1038/ncomms7601
Abstrakt: 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.
Databáze: MEDLINE