Expression quantitative trait locus mapping of extracellular microRNAs in human plasma

被引：0

作者：

Huan, Tianxiao ^{[1
,2
]}

Joehanes, Roby ^{[1
,2
]}

Rong, Jian ^{[3
]}

Chen, Ming-Huei ^{[1
,2
]}

Mustafa, Rima ^{[4
]}

Dehghan, Abbas ^{[4
,6
]}

Ghanbari, Mohsen ^{[5
]}

Karlin, Hannah ^{[1
,2
]}

Hwang, Shih-Jen ^{[1
,2
]}

Courchesne, Paul ^{[1
,2
]}

Larson, Martin G. ^{[3
]}

Johnson, Andrew D. ^{[1
,2
]}

Freedman, Jane E. ^{[5
,7
]}

Levy, Daniel ^{[1
,2
]}

机构：

[1] NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA

[2] NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20824 USA

[3] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA

[4] Imperial Coll London, Dept Epidemiol & Biostat, London SW7 2AZ, England

[5] Erasmus MC Univ Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[6] Imperial Coll London, MRC Ctr Environm & Hlth, London SW7 2AZ, England

[7] Vanderbilt Univ, Sch Med, 1161 21st Ave S, Nashville, TN 37232 USA

来源：

ISCIENCE | 2024年 / 27卷 / 10期

基金：

美国国家卫生研究院;

关键词：

MENDELIAN RANDOMIZATION; REACTIVITY; BIOMARKERS;

D O I：

10.1016/j.isci.2024.110988

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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