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.
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页数：16
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