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
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.
