Genetic variants could influence the transcription and function of miRNAs, which may affect miRNA-mediated gene regulation and lead to phenotypes and diseases. Integration of genomics and miRNAs data enables interrogation of the genetic architecture of miRNAs, revealing their clinical importance, and providing valuable resources for future studies on clinical significance of miRNAs in human disease. Here we present the results of genome-wide association studies on >2000 circulating miRNAs in plasma measured by RNA-sequencing in the Rotterdam Study (Phase 1). We report both cis and trans  miRNA-expression quantitative trait loci (miRNA-eQTLs) at the nominal significance level (p-value < 0.05) and those that have been replicated across two independent cohorts (see Ref below). The consequences of perturbation in miRNA transcription on a wide range of clinical conditions are systematically investigated in phenome-wide association studies, with their causality tested using Mendelian randomization in the UK Biobank. Moreover, we found several miRNA-eQTLs overlapping with gene expression, protein, and metabolite-QTLs and with disease-associated variants reported in previous GWAS studies (see the disease association and omics integration parts).