MicroRNA-guided prioritization of genome-wide association signals reveals the importance of microRNA-target gene networks for complex traits in cattle

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  • Lingzhao Fang, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture &National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, 100193, Beijing, China., Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742., Animal Genomics and Improvement Laboratory, Agricultural Research Service, USDA
  • ,
  • Peter Sørensen
  • Goutam Sahana
  • Frank Panitz
  • Guosheng Su
  • Shengli Zhang, College of Animal Science and Technology, China Agricultural University, China Agricultural University, China
  • Ying Yu, College of Animal Science and Technology, China Agricultural University, Denmark
  • Bingjie Li
  • ,
  • Li Ma, Department of Animal and Avian Sciences, University of Maryland, College Park, 20742 MD, USA
  • ,
  • George Liu, Animal Genomics and Improvement Laboratory, ARS USDA, Beltsville, 207052350 MD, USA
  • ,
  • Mogens Sandø Lund
  • Bo Thomsen
MicroRNAs (miRNA) are key modulators of gene expression and so act as putative fine-tuners of complex phenotypes. Here, we hypothesized that causal variants of complex traits are enriched in miRNAs and miRNA-target networks. First, we conducted a genome-wide association study (GWAS) for seven functional and milk production traits using imputed sequence variants (13~15 million) and >10,000 animals from three dairy cattle breeds, i.e., Holstein (HOL), Nordic red cattle (RDC) and Jersey (JER). Second, we analyzed for enrichments of association signals in miRNAs and their miRNA-target networks. Our results demonstrated that genomic regions harboring miRNA genes were significantly (P < 0.05) enriched with GWAS signals for milk production traits and mastitis, and that enrichments within miRNA-target gene networks were significantly higher than in random gene-sets for the majority of traits. Furthermore, most between-trait and across-breed correlations of enrichments with miRNA-target networks were significantly greater than with random gene-sets, suggesting pleiotropic effects of miRNAs. Intriguingly, genes that were differentially expressed in response to mammary gland infections were significantly enriched in the miRNA-target networks associated with mastitis. All these findings were consistent across three breeds. Collectively, our observations demonstrate the importance of miRNAs and their targets for the expression of complex traits.
Original languageEnglish
Article number9345
JournalScientific Reports
Volume8
Number of pages14
ISSN2045-2322
DOIs
Publication statusPublished - 19 Jun 2018

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