Expression quantitative trait locus mapping of extracellular microRNAs in human plasma

Tianxiao Huan; Roby Joehanes; Jian Rong; Ming-Huei Chen; Rima Mustafa; Abbas Dehghan; Mohsen Ghanbari; Hannah Karlin; Shih-Jen Hwang; Paul Courchesne; Martin G. Larson; Andrew D. Johnson; Jane E. Freedman; Daniel Levy

iScience (Oct 2024)

Expression quantitative trait locus mapping of extracellular microRNAs in human plasma

Tianxiao Huan,
Roby Joehanes,
Jian Rong,
Ming-Huei Chen,
Rima Mustafa,
Abbas Dehghan,
Mohsen Ghanbari,
Hannah Karlin,
Shih-Jen Hwang,
Paul Courchesne,
Martin G. Larson,
Andrew D. Johnson,
Jane E. Freedman,
Daniel Levy

Affiliations

Tianxiao Huan: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA; Corresponding author
Roby Joehanes: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Jian Rong: Department of Mathematics and Statistics, Boston University, Boston, MA 02118, USA
Ming-Huei Chen: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Rima Mustafa: Department of Epidemiology and Biostatistics, Imperial College London, London SW7 2AZ, UK
Abbas Dehghan: Department of Epidemiology and Biostatistics, Imperial College London, London SW7 2AZ, UK; MRC Centre for Environment and Health, Imperial College London, London SW7 2AZ, UK
Mohsen Ghanbari: Department of Epidemiology, Erasmus MC University Medical Center, 3000 CA Rotterdam, the Netherlands
Hannah Karlin: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Shih-Jen Hwang: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Paul Courchesne: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Martin G. Larson: Department of Mathematics and Statistics, Boston University, Boston, MA 02118, USA
Andrew D. Johnson: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA
Jane E. Freedman: School of Medicine, Vanderbilt University, 1161 21st Avenue S, Nashville, TN 37232, USA
Daniel Levy: The National Heart, Lung, and Blood Institute’s Framingham Heart Study, 73 Mt. Wayte Avenue, Framingham, MA 01702, USA; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20824, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 10
p. 110988

Abstract

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Summary: MicroRNAs, crucial in regulating protein-coding gene expression, are implicated in various diseases. We performed a genome-wide association study of plasma miRNAs (ex-miRNAs) in 3,743 Framingham Heart Study (FHS) participants and identified 1,027 cis-ex-miRNA-eQTLs (cis-exQTLs) for 37 ex-miRNAs, with 55% replication in an independent study. Colocalization analyses suggested potential genetic coregulation of ex-miRNAs with whole blood mRNAs. Mendelian randomization indicated 29 ex-miRNAs potentially influencing 35 traits. Notably, the chromosome 14q23 and 14q32 miRNA clusters emerged as the top signal, contributing over 50% of the significant cis-exQTL results, and were associated with a diverse range of traits including platelet count. Correlations of 10 ex-miRNAs (such as miR-376c-3p) in 14q32 with platelet count and volume were confirmed in FHS participants. These findings shed light on the genetic basis of ex-miRNA expression and their involvement in complex traits.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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