Development of the novel drug repositioning method based on disease genetics

• Project/Area Number: 15K14429
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: Osaka University (2016); Tokyo Medical and Dental University (2015)
• Principal Investigator: OKADA YUKINORI 大阪大学, 医学系研究科, 教授 (70727411)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝統計学 / ドラッグ・リポジショニング / ゲノム創薬

Outline of Final Research Achievements

In this study, we constructed an in silico analytical method that utilizes large scale human disease genome analysis results to efficiently identify novel therapeutic targets and candidates of drug repositioning. We collected drug and drug target gene information from multiple drug discovery databases. We also curated Anatomical Therapeutic Chemical (ATC) Classification System to list disease and approved drug lists. By applying the newly constructed method to the latest disease genetics study results of multiple human diseases including metabolic diseases, we empirically evaluated the value of our method.

Research Products

• [Int'l Joint Research] Harvard Medical School/Broad Institute(USA)
• [Int'l Joint Research] Sanger Institute(England)
• [Journal Article] The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1. (2016)
  • Author(s): Li G, Cunin P, Wu D, Diogo D, Yang Y, Okada Y, Plenge RM, Nigrovic PA
  • Journal Title: PLoS Genet Volume: 12
  • DOI: 10.1371/journal.pgen.1006292
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity. (2016)
  • Author(s): Mahajan A, Rodan AR, Le TH, Gaulton KJ, Haessler J, ..., Okada Y, Laurie CC, Morris AP, Franceschini N
  • Journal Title: Am J Hum Gen Volume: 99 Pages: 636-646
  • DOI: 10.1016/j.ajhg.2016.07.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of variations in HLA class Ⅱ and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. (2016)
  • Author(s): Shiraishi K, Takahashi A, Takano A, Watanabe Y, Hishida T, Tsuchihara K, Miyagi Y, Tanaka K, Imai K, Minamiya Y, Sakamoto H, Inazawa J, Nakamura Y, Yoshida T, Yokota J, Matsuda F, Matsuo K, Daigo Y, Kubo M, Kohno T, et. al.
  • Journal Title: Nature Communications Volume: 7 Pages: 12451-12451
  • DOI: 10.1038/ncomms12451
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis. (2016)
  • Author(s): Okada Y, Suzuki A, Ikari K, Terao C, Kochi Y, Ohmura K, Higasa K, Akiyama M, Ashikawa K, Kanai M, Hirata J, Suita N, Teo YY, Xu H, Bae SC, Takahashi A, Momozawa Y, Matsuda K, Momohara S, Taniguchi A, Yamada R, Mimori T, Kubo M, Brown MA, Raychaudhuri S, Matsuda F, Yamanaka H, Kamatani Y, Yamamoto K
  • Journal Title: Am J Hum Genet. Volume: 99 Pages: 366-374
  • DOI: 10.1016/j.ajhg.2016.06.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study. (2016)
  • Author(s): Li Z, Xia Y, Feng LN, Chen JR, Li HM, Cui J, Cai QQ, Sim KS, ..., Okada Y, Raychaudhuri S, Lim ST, Tan W, Peng RJ, Khor CC, Bei JX
  • Journal Title: Lancet Oncol Volume: 17 Pages: 1240-1247
  • DOI: 10.1016/s1470-2045(16)30148-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set (2016)
  • Author(s): Kanai M, Tanaka T, Okada Y
  • Journal Title: J Hum Genet Volume: 61 Pages: 861-866
  • DOI: 10.1038/jhg.2016.72
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes. (2016)
  • Author(s): Fujimoto A, Okada Y, Boroevich KA, Tsunoda T, Taniguchi H, Nakagawa H
  • Journal Title: Sci Repdoi:10.1038/srep26483 Volume: 6 Pages: 26483-26483
  • DOI: 10.1038/srep26483
  • Peer Reviewed / Open Access
• [Journal Article] Significant impact of miRNA-target gene networks on genetics of human complex traits (2016)
  • Author(s): Okada Y, Muramatsu T, Suita N, Kanai M, Kawakami E et al.
  • Journal Title: Scientific Reports Volume: 6 Pages: 22223-22223
  • DOI: 10.1038/srep22223
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry. (2016)
  • Author(s): 76.Imamura M, Takahashi A, Yamauchi T, Hara K, Yasuda K, ... Okada Y et al.
  • Journal Title: Nat Genet. Volume: 48 Pages: 323-330
  • DOI: 10.1038/ng.3496
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ethnically shared and heterogeneous impacts of molecular pathways suggested by the genome-wide meta-analysis of rheumatoid arthritis. (2016)
  • Author(s): Okada Y, Raj T, Yamamoto K.
  • Journal Title: Rheumatology (Oxford) Volume: 22 Pages: 186-189
  • DOI: 10.1093/rheumatology/kev314
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese (2015)
  • Author(s): Okada Y, Momozawa Y, Ashikawa K, Kanai M, Matsuda K et al.
  • Journal Title: Nature Genetics Volume: 42 Pages: 798-802
  • DOI: 10.1038/ng.3310
  • Peer Reviewed / Open Access / Int'l Joint Research