@article{Okada2016,
abstract = {AbstractThe 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.},
author = {Okada, Yukinori and Muramatsu, Tomoki and Suita, Naomasa and Kanai, Masahiro and Kawakami, Eiryo and Iotchkova, Valentina and Soranzo, Nicole and Inazawa, Johji and Tanaka, Toshihiro},
doi = {10.1038/srep22223},
journal = {Scientific Reports},
month = {mar},
title = {Significant impact of miRNA–target gene networks on genetics of human complex traits},
url = {http://dx.doi.org/10.1038/srep22223},
volume = {6},
year = {2016}
}