Abstract
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. Here we present a miR-eQTL mapping study of whole blood from 5239 individuals, and identify 5269 cis-miR-eQTLs for 76 mature microRNAs. Forty-nine percent of cis-miR-eQTLs are located 300–500kb upstream of their associated intergenic microRNAs, suggesting that distal regulatory elements may affect the interindividual variability in microRNA expression levels. We find that cis-miR-eQTLs are highly enriched for cis-mRNA-eQTLs and regulatory SNPs. Among 243 cis-miR-eQTLs that were reported to be associated with complex traits in prior genome-wide association studies, many cis-miR-eQTLs miRNAs display differential expression in relation to the corresponding trait (e.g., rs7115089, miR-125b-5p, and HDL cholesterol). Our study provides a roadmap for understanding the genetic basis of miRNA expression, and sheds light on miRNA involvement in a variety of complex traits.
Highlights
Identification of microRNA expression quantitative trait loci can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits
By cross-linking cismiR-expression quantitative trait locus (eQTL) single nucleotide polymorphisms (SNPs) with regulatory SNPs annotated by the ENCODE project[20] and with complex trait-associated SNPs identified in prior genome-wide association studies (GWAS)[21,22], and by linking cis-miRNA Ct values (miR)-eQTL miRNAs with differentially expressed miRNAs for complex traits, we sought to dissect the genetic regulation of miRNA expression and explore the extent to which cis-miR-eQTLs may affect interindividual phenotype variability
NAs that were expressed in 4200 participants, of these 247 miRNAs were expressed in
Summary
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. We analyze the associations of B10 million 1000 Genomes Project[19] imputed single nucleotide polymorphisms (SNPs) (at minor allele frequency (MAF) 40.01 and imputation quality ratio 40.1) with whole blood-derived miRNA expression levels of 280 mature miRNAs expressed in 4200 individuals, representing 11% of all discovered human miRNAs to date (2,576 mature miRNAs have been reported in miRbase v20: www.mirbase.org). We calculate both cis- and trans-miR-eQTLs genome wide, and identify cis-miR-eQTLs with concordant effects in two pedigree independent study groups. The miR-eQTLs from the model that adjusted for imputed cell counts in the larger set of 5,024 participants are provided in Supplementary Data 5
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