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 Cleaning Kit 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 Vitamins 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.