Integrative application of human and Mycobacterium tuberculosis genomic information to identify genetic risk factors for tuberculosis onset shared among different populations

• Project/Area Number: 18K15041
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: National Center for Global Health and Medicine (2019-2020); The University of Tokyo (2018)
• Principal Investigator: Omae Yosuke 国立研究開発法人国立国際医療研究センター, その他部局等, 特任研究員 (70722552)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ゲノムワイド関連解析 / ヒトゲノム / 病原体ゲノム / 結核 / 感染症 / 病原菌ゲノム

Outline of Final Research Achievements

We have conducted stratified analyses in tuberculosis (TB), which is one of the three major global infectious diseases caused by pathogenic bacterium, Mycobacterium tuberculosis (MTB), and have already reported specific association of pathogen lineage group and host genetic risk factors with TB onset and disease outcome. In this research project, we first collected both human genome-wide SNP data and MTB whole genome sequencing (WGS) data from newly recruited Thai TB patients. We also collected the human and MTB data from Japanese TB patients and combined the Thai and Japanese datasets to further identify specific association of human and pathogen genome variations with patient disease onset and clinical characteristics in our genome-wide association study (GWAS) approach.　Our approaches identified shared genetic risk factors among different populations and can become a breakthrough for research strategy in infectious diseases based on patient genomic and pathogen genomic information.

Academic Significance and Societal Importance of the Research Achievements

感染症は、宿主である患者側ヒトゲノムの多様性と同時に、病原体の感染という環境要因が重要である。結核患者のゲノム情報とその感染結核菌のゲノム情報を両面から解析することにより、異なる集団間で共通する結核発症において重要な宿主の遺伝要因および結核菌のゲノム変異を同定した。本研究で用いた宿主ゲノム情報と病原体ゲノム情報の両方に基づく解析アプローチは、結核以外の感染症にも応用可能であり、感染症研究のブレークスルーになる可能性を秘めている。

Research Products

• [Int'l Joint Research] タイ保健省医科学局/マヒドン大学(タイ)
• [Int'l Joint Research] タイ保健省医科学局/マヒドン大学(タイ)
• [Int'l Joint Research] タイ国保健省医科学局/国立マヒドン大学(タイ)
• [Journal Article] Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease (2021)
  • Author(s): Ho Namkoong, Yosuke Omae, Takanori Asakura, Makoto Ishii, Shoji Suzuki, Kozo Morimoto, Yosuke Kawai, Katsura Emoto, Andrew J. Oler, Eva P. Szymanski, Mitsunori Yoshida, et al.
  • Journal Title: European Respiratory Journal Volume: 57 Issue: 2 Pages: 1902269-1902269
  • DOI: 10.1183/13993003.02269-2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 感染病ゲノム解析の最前線―COVID-19のゲノムワイド関連解析を例としてー (2021)
  • Author(s): 大前陽輔、徳永勝士
  • Journal Title: 遺伝学医学 Volume: 11(2) Pages: 48-55
  • Peer Reviewed
• [Journal Article] Genomewide Association Study Confirming the Association of NAT2 with Susceptibility to Antituberculosis Drug-Induced Liver Injury in Thai Patients (2019)
  • Author(s): Suvichapanich S, Wattanapokayakit S, Mushiroda T, Yanai H, Chuchottawon C, Kantima T, Nedsuwan S, Suwankesawong W, Sonsupap C, Pannarunothai R, Tumpattanakul S, Bamrungram W, Chaiwong A, Mahasirimongkol S, Mameechai S, Panthong W, Klungtes N, Munsoo A, Chauychana U, Maneerat M, Fukunaga K, Omae Y, Tokunaga K
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 63 Issue: 8 Pages: 2692-2718
  • DOI: 10.1128/aac.02692-18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Host genetic risk factors for infectious diseases identified through genome-wide analyses / ヒトゲノム全域の解析からみえてきた感染症の発症遺伝要因 (2018)
  • Author(s): Omae Y, Tokunaga K.
  • Journal Title: 医学のあゆみ Volume: 266(6) Pages: 466-472
  • Peer Reviewed
• [Presentation] Mycobacterium tuberculosis identified from pathogen lineage based genome-wide association study in tuberculosis (2018)
  • Author(s): Omae Y, Toyo-oka L, Mahasirimongkol S, Yanai H, Smittipat N, Palittapongarnpim P, Nedsuwan S, Wattanapokayakit S, Satproedprai N, Sawanpanyalert P, Inunchot W, Pasomsub E, Wichukchinda N, Mushiroda T, Kubo M, Tokunaga K
  • Organizer: American Society of Human Genetics (ASHG)
  • Int'l Joint Research
• [Presentation] A novel susceptibility locus CD53 in tuberculosis identified by pathogen lineage-based genome-wide association study (2018)
  • Author(s): Tokunaga K, Omae Y, Toyo-oka L, Yanai1 H, Wattanapokayakit S, Smittipat N, Palittapongarnpim P, Wichukchinda N, Mushiroda T, Mahasirimongkol S
  • Organizer: European Society of Human Genetics (ESHG)
  • Int'l Joint Research
• [Presentation] Pathogen lineage based genome-wide association study in tuberculosis revealed interplay among host and pathogen genomes (2018)
  • Author(s): Omae Y, Toyo-oka L, Mahasirimongkol S, Yanai H, Smittipat N, Palittapongarnpim P, Nedsuwan S, Wattanapokayakit S, Satproedprai N, Sawanpanyalert P, Inunchot W, Pasomsub E, Wichukchinda N, Mushiroda T, Kubo M, Tokunaga K
  • Organizer: Japan Society of Human Genetics (JSHG)/日本人類遺伝学会総会
• [Book] Genetics of Infectious Diseases. In: Tsunoda T., Tanaka T., Nakamura Y. (eds) Genome-Wide Association Studies. (2019)
  • Author(s): Omae Y and Tokunaga K.
  • Total Pages: 30
  • Publisher: Springer, Singapore
  • ISBN: 9789811381775
• [Remarks] ゲノム医科学プロジェクト（戸山）ホームページ＞研究内容＞結核研究
  • URL: http://genome-toyama.ncgm.go.jp/researches/tuberculosis.html
• [Remarks] ゲノム医科学プロジェクト（戸山）ホームページ＞研究内容＞結核研究
  • URL: http://genome-toyama.jp/researches/tuberculosis