Comprehensive analysis of inflammatory bowel disease using by genome-wid genetic and epigenetic association studies

• Project/Area Number: 26293180
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nihon University (2016-2017); Institute of Physical and Chemical Research (2014-2015)
• Principal Investigator: YAMAZAKI Keiko 日本大学, 医学部, 助教 (50415329)
• Co-Investigator(Kenkyū-buntansha): 鈴木 康夫 東邦大学, 医学部, 教授 (40261911) ; 江崎 幹宏 九州大学, 大学病院, 講師 (50335957) ; 梅野 淳嗣 九州大学, 大学病院, 助教 (70621704) ; LOW SIEWKEE 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (40634720)
• Research Collaborator: MOTOYA Satoshi ; FUYUNO Yuta
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 炎症性腸疾患 / 全ゲノム関連解析 / 薬剤応答性 / エピゲノム解析 / 薬剤反応性

Outline of Final Research Achievements

The aim of this project is to clarify the pathogenesis of inflammatory bowel disease (IBD) using by analysis of genome-wide genetic and epigenetic association. Since it is difficult to design using whole-genome epigenetic analysis for multifactorial disease except cancer, we focus the response of anti TNF-α monoclonal antibody in IBD. We have rescrueted patients with IBD who were treated with anti TNF-α antibody for the first time and examined methylation assays including whole-genome bisulfite sequncing.
Furthermore, we collaborated with the International IBD Genetics Consortium and conducted transancestry association study of IBD. Out trans-ethinic genome-wide association study clarified that the direction and magnitude of effect are consistent in European and non-European cohorts in spite of the genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency or effect size.

Research Products

• [Int'l Joint Research] University of Delhi South Campus/Deyanand Medical College and Hospital(インド)
• [Int'l Joint Research] University Medical Centre Groningen(オランダ)
• [Journal Article] Intestinal Epithelial Cell-specific Deletion of α-Mannosidase II Ameliorates Experimental Colitis (2018)
  • Author(s): Suzuki K., Yamada T, Yamazaki K, Hirota M, Ishihara N, Sakamoto M, Takahashi D, Iijima H, Hase K.
  • Journal Title: Cell Structure and Function Volume: 43 Issue: 1 Pages: 25-39
  • DOI: 10.1247/csf.17022
  • NAID: 130006513071
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access
• [Journal Article] A cross-ethnic survey of CFB and SLC44A4, Indian ulcerative colitis GWAS hits, underscores their potential role in disease susceptibility (2016)
  • Author(s): Gupta Aditi、Juyal Garima、Sood Ajit、Midha Vandana、Yamazaki Keiko、Vich Vila Arnau、Esaki Motohiro、Matsui Toshiyuki、Takahashi Atsushi、Kubo Michiaki、Weersma Rinse K、Thelma B K
  • Journal Title: European Journal of Human Genetics Volume: 25 Issue: 1 Pages: 111-122
  • DOI: 10.1038/ejhg.2016.131
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Disease susceptibility genes shared by primary biliary cirrhosis and Crohn’s disease in the Japanese population (2015)
  • Author(s): Yoshihiro Aiba, Keiko Yamazaki, Nao Nishida, Minae Kawashima, Yuki Hitomi, Hitomi Nakamura, Atsumasa Komori, Yuta Fuyuno, Atsushi Takahashi, Takaaki Kawaguchi, Masakazu Takazoe, Yasuo Suzuki, Satoshi Motoya Toshiyuki Matsui Motohiro Esaki, Takayuki Matsumoto, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura
  • Journal Title: Journal of Human Genetics Volume: 印刷中 Issue: 9 Pages: 525-531
  • DOI: 10.1038/jhg.2015.59
  • NAID: 40020589506
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations (2015)
  • Author(s): Liu JZ, van Sommeren S, Huang H et.al
  • Journal Title: Nat Genet Volume: 47 Issue: 9 Pages: 979-86
  • DOI: 10.1038/ng.3359
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic characteristics of inflammatory bowel disease in a Japanese population. (2015)
  • Author(s): Fuyuno Y, Yamazaki K, Takahashi A, Esaki M, Kawaguchi T, Takazoe M, Matsumoto T, Matsui T, Tanaka H, Motoya S, Suzuki Y, Kiyohara Y, Kitazono T, Kubo M.
  • Journal Title: J Gastroenterol. Volume: 不明
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 炎症性腸疾患関連遺伝子解明の現状と将来展望 (2014)
  • Author(s): 山崎 慶子
  • Organizer: 第６回 日本炎症性腸疾患研究会学術集会
  • Place of Presentation: 品川 (日本)
  • Year and Date: 2014-12-14
  • Invited
• [Presentation] A genome-wide association study by using imputed genotypes identifies a susceptibility locus for Crohn's disease in a Japanese population (2014)
  • Author(s): Yamazaki K, Umeno J, Takahashi A, Hirano A, Johnson T, Morizono T, Kawaguchi T, Takazoe M, Yamada T, Suzuki Y, Tanaka H, Motoya S, Hosokawa M, Arimura Y, Shinomura Y, Matsui T, Matsumoto T, Iida M, Tsunoda T, Nakamura Y, Kamatani N, Kubo M
  • Organizer: ASHG (The American Society of Human Genetics) 61th Annual Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-10-18 – 2014-10-22