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

doi:10.1016/j.isci.2024.110988

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^*

^*Corresponding author for this work

Epidemiology

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	110988
Journal	iScience
Volume	27
Issue number	10
DOIs	https://doi.org/10.1016/j.isci.2024.110988
Publication status	Published - 18 Oct 2024

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Expression quantitative trait locus mapping of extracellular microRNAs in human plasmaFinal published version, 3.36 MBLicence: CC BY-NC-ND

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title = "Expression quantitative trait locus mapping of extracellular microRNAs in human plasma",

abstract = "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.",

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

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doi = "10.1016/j.isci.2024.110988",

language = "English",

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T1 - Expression quantitative trait locus mapping of extracellular microRNAs in human plasma

AU - Huan, Tianxiao

AU - Joehanes, Roby

AU - Rong, Jian

AU - Chen, Ming Huei

AU - Mustafa, Rima

AU - Dehghan, Abbas

AU - Ghanbari, Mohsen

AU - Karlin, Hannah

AU - Hwang, Shih Jen

AU - Courchesne, Paul

AU - Larson, Martin G.

AU - Johnson, Andrew D.

AU - Freedman, Jane E.

AU - Levy, Daniel

PY - 2024/10/18

Y1 - 2024/10/18

N2 - 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.

AB - 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.

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DO - 10.1016/j.isci.2024.110988

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VL - 27

JO - iScience

JF - iScience

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Expression quantitative trait locus mapping of extracellular microRNAs in human plasma

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