title: Genome-wide identification of microRNA expression quantitative trait loci.
abstract: 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.
authors: 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.
authors: Tianxiao
authors: T
authors: Huan
authors: Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02118, USA.
authors: Jian
authors: J
authors: Rong
authors: 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.
authors: Chunyu
authors: C
authors: Liu
authors: 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.
authors: Xiaoling
authors: X
authors: Zhang
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors: Kahraman
authors: K
authors: Tanriverdi
authors: 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.
authors: Roby
authors: R
authors: Joehanes
authors: 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.
authors: Brian H
authors: BH
authors: Chen
authors: 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.
authors: Joanne M
authors: JM
authors: Murabito
authors: 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.
authors: Chen
authors: C
authors: Yao
authors: 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.
authors: Paul
authors: P
authors: Courchesne
authors: Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20824, USA.
authors: Peter J
authors: PJ
authors: Munson
authors: 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.
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
authors: Nancy
authors: N
authors: Cox
authors: 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.
authors: Andrew D
authors: AD
authors: Johnson
authors: 1] The Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02118, USA.
authors: Martin G
authors: MG
authors: Larson
authors: 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.
authors: Daniel
authors: D
authors: Levy
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors: Jane E
authors: JE
authors: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs