Genome-wide association study of peripheral arterial disease

• Project/Area Number: 25462159
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Miyata Tetsuro 東京大学, 医学部附属病院, 登録研究員 (70190791)
• Co-Investigator(Kenkyū-buntansha): HOSAKA Akihiro 東京大学, 医学部附属病院, 助教 (90625170) ; 宮原 拓也 東京大学, 医学部附属病院, 助教 (20704943)
• Co-Investigator(Renkei-kenkyūsha): MIYAHARA Takuya 東京大学, 医学部附属病院, 助教 (20704943)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: PAD / GWAS / 閉塞性動脈硬化症 / ゲノムワイド関連解析

Outline of Final Research Achievements

Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,754 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10-14, 5.3 x 10-9 and 8.8 x 10-8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

Research Products

• [Journal Article] Genome-Wide Association Study of Peripheral Arterial Disease in a Japanese Population (2015)
  • Author(s): Matsukura M, Ozaki K, Takahashi A, Onouchi Y, Miyata T, et al
  • Journal Title: PLOS ONE Volume: オープンジャーナル Issue: 10 Pages: 1-13
  • DOI: 10.1371/journal.pone.0139262
  • Peer Reviewed
• [Presentation] 「閉塞性動脈硬化症の全エクソーム解析」 (2015)
  • Author(s): 松倉 満
  • Organizer: 第56回日本脈管学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都港区）
  • Year and Date: 2015-10-30