title: MicroRNA expression in abdominal and gluteal adipose tissue is associated with mRNA expression levels and partly genetically driven.
abstract: To understand how miRNAs contribute to the molecular phenotype of adipose tissues and related traits, we performed global miRNA expression profiling in subcutaneous abdominal and gluteal adipose tissue of 70 human subjects and characterised which miRNAs were differentially expressed between these tissues. We found that 12% of the miRNAs were significantly differentially expressed between abdominal and gluteal adipose tissue (FDR adjusted p<0.05) in the primary study, of which 59 replicated in a follow-up study of 40 additional subjects. Further, 14 miRNAs were found to be associated with metabolic syndrome case-control status in abdominal tissue and three of these replicated (primary study: FDR adjusted p<0.05, replication: p<0.05 and directionally consistent effect). Genome-wide genotyping was performed in the 70 subjects to enable miRNA expression quantitative trait loci (eQTL) analysis. Candidate miRNA eQTLs were followed-up in the additional 40 subjects and six significant, independent cis-located miRNA eQTLs (primary study: p<0.001; replication: p<0.05 and directionally consistent effect) were identified. Finally, global mRNA expression profiling was performed in both tissues to enable association analysis between miRNA and target mRNA expression levels. We find 22% miRNAs in abdominal and 9% miRNAs in gluteal adipose tissue with expression levels significantly associated with the expression of corresponding target mRNAs (FDR adjusted p<0.05). Taken together, our results indicate a clear difference in the miRNA molecular phenotypic profile of abdominal and gluteal adipose tissue, that the expressions of some miRNAs are influenced by cis-located genetic variants and that miRNAs are associated with expression levels of their predicted mRNA targets.
authors.affiliation: Department of Statistics, University of Oxford, Oxford, United Kingdom.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Herrera
authors.forename: George
authors.initials: G
authors.lastname: Nicholson
authors.forename: Rory
authors.initials: R
authors.lastname: Bowden
authors.forename: Quin F
authors.initials: QF
authors.lastname: Wills
authors.forename: Josine L
authors.initials: JL
authors.lastname: Min
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Neville
authors.forename: Amy
authors.initials: A
authors.lastname: Barrett
authors.forename: Maxine
authors.initials: M
authors.lastname: Allen
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Krina T
authors.initials: KT
authors.lastname: Zondervan
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.forename: Chris C
authors.initials: CC
authors.lastname: Holmes
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
mesh_terms: D050153:Abdominal Fat / Q000502:physiology*; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D002081:Buttocks / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger
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