Huan Tianxiao, Joehanes Roby, Rong Jian, Chen Ming-Huei, Mustafa Rima, Dehghan Abbas, Ghanbari Mohsen, Karlin Hannah, Hwang Shih-Jen, Courchesne Paul, Larson Martin G, Johnson Andrew D, Freedman Jane E, Levy Daniel
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.
iScience. 2024 Sep 18;27(10):110988. doi: 10.1016/j.isci.2024.110988. eCollection 2024 Oct 18.
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 ex-miRNA-eQTLs (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 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.
微小RNA在调节蛋白质编码基因表达中起关键作用，与多种疾病有关。我们对3743名弗雷明汉心脏研究（FHS）参与者的血浆微小RNA（外泌体微小RNA）进行了全基因组关联研究，确定了37种外泌体微小RNA的1027个外泌体微小RNA表达数量性状基因座（外显子QTL），在一项独立研究中的重复率为55%。共定位分析表明外泌体微小RNA与全血信使核糖核酸存在潜在的基因共调控。孟德尔随机化表明29种外泌体微小RNA可能影响35种性状。值得注意的是，14号染色体q23和14号染色体q32微小RNA簇成为最显著的信号，贡献了超过50%的显著外显子QTL结果，并且与包括血小板计数在内的多种性状相关。在FHS参与者中证实了14号染色体q32上10种外泌体微小RNA（如miR-376c-3p）与血小板计数和体积的相关性。这些发现揭示了外泌体微小RNA表达的遗传基础及其在复杂性状中的作用。
