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

Yukinori Okada, Tomoki Muramatsu, Naomasa Suita, Masahiro Kanai, Eiryo Kawakami, Valentina Iotchkova, Nicole Soranzo, Johji Inazawa, Toshihiro Tanaka

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 (P < 0.05/18 = 0.0028, most significant enrichment in RA with P = 1.7 × 10-4). Interestingly, these results were consistent with current literature-based knowledge of the traits on miRNA obtained through the NCBI PubMed database search (adjusted P = 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 PADI2, a novel RA risk gene considered as a promising therapeutic target (rs761426, adjusted P = 2.3 × 10-9). 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.

Original languageEnglish
Article number22223
JournalScientific Reports
StatePublished - 1 Mar 2016
Externally publishedYes


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