Significant impact of miRNA–target gene networks on genetics of human complex traits

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書誌事項

公開日
2016-03-01
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/srep22223
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>The impact of microRNA (miRNA) on the genetics of human complex traits, especially in the context of miRNA-target gene networks, has not been fully assessed. Here, we developed a novel analytical method, MIGWAS, to comprehensively evaluate enrichment of genome-wide association study (GWAS) signals in miRNA–target gene networks. We applied the method to the GWAS results of the 18 human complex traits from >1.75 million subjects and identified significant enrichment in rheumatoid arthritis (RA), kidney function and adult height (<jats:italic>P </jats:italic>< 0.05/18= 0.0028, most significant enrichment in RA with <jats:italic>P </jats:italic>= 1.7 × 10<jats:sup>−4</jats:sup>). Interestingly, these results were consistent with current literature-based knowledge of the traits on miRNA obtained through the NCBI PubMed database search (adjusted <jats:italic>P </jats:italic>= 0.024). Our method provided a list of miRNA and target gene pairs with excess genetic association signals, part of which included drug target genes. We identified a miRNA (miR-4728-5p) that downregulates <jats:italic>PADI2</jats:italic>, a novel RA risk gene considered as a promising therapeutic target (rs761426, adjusted <jats:italic>P </jats:italic>= 2.3 × 10<jats:sup>−9</jats:sup>). Our study indicated the significant impact of miRNA–target gene networks on the genetics of human complex traits and provided resources which should contribute to drug discovery and nucleic acid medicine.</jats:p>

収録刊行物

  • Scientific Reports

    Scientific Reports 6 (1), 22223-, 2016-03-01

    Springer Science and Business Media LLC

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