Genome-Wide Association study of Progression in Adolescent Idiopathic Scoliosis

• Project/Area Number: 18H02931
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Inaba Ikuyo 国立研究開発法人理化学研究所, 生命医科学研究センター, 客員研究員 (60415081)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 思春期特発性側弯症 / 全ゲノム関連解析 / 一塩基多型 / 多因子遺伝病 / 疾患感受性遺伝子 / 側弯 / 遺伝子 / ゲノム / 疾患感受性遺伝 / 全ゲノム相関解析 / ビッグデータ / 疾患関連遺伝子

Outline of Final Research Achievements

Adolescent idiopathic scoliosis (AIS) is the most common pediatric disease affecting spine. Large-scale genome analyses of AIS were performed. An international meta-analysis of previously identified gene loci associated with progression and aggravation of AIS was performed using multiracial samples to confirm the reproducibility of susceptibility gene loci. In addition, a new AIS Genome-Wide Association Study (GWAS) was performed using approximately 3,200 AIS patient samples and approximately 60,000 non-patient samples collected so far. A meta-analysis was performed in which the obtained data was integrated with the GWAS data of the two AISs performed earlier in my lab.

Academic Significance and Societal Importance of the Research Achievements

AISは人口の2-4%に発症するcommon diseaseである。非成人の骨関節疾患で最も頻度が高い疾患で、法律によりその検診が義務付けられているほど、社会の大問題となっている。遺伝要因と環境要因の相互作用により発症する多因子遺伝病であると考えられており、その発症、進行には遺伝要因が深く関与することが明らかになっている。
AISは、側弯の進行度合いに応じて治療方法が異なり、進行すると治療が困難となるため、早期発見と進行予測が重要である。今回、AISの進行・重症化に関与する遺伝子を新たに同定したので、同定した遺伝子の機能解析研究を突破口に、AISの病態の分子レべルでの解明に繋げたい。

Research Products

• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] University of Hong Kong/Nanjing Drum Tower Hospital(中国)
• [Journal Article] Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases (2020)
  • Author(s): Ishigaki K, Akiyama M, Kanai M, Takahashi A, Kawakami E, Sugishita H, Sakaue S, Matoba N, Low SK, Okada Y, Yamaji T, et al
  • Journal Title: Nature Genetics Volume: 52 Issue: 7 Pages: 669-679
  • DOI: 10.1038/s41588-020-0640-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese (2019)
  • Author(s): Kou Ikuyo、Otomo Nao、Takeda Kazuki、Momozawa Yukihide、et al
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41467-019-11596-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis (2019)
  • Author(s): Takeda Kazuki, Otomo Nao, Ogura Yoji, Takahashi Yohei, Matsumoto Morio, Watanabe Kota et al
  • Journal Title: Journal of Human Genetics Volume: 64 Issue: 5 Pages: 493-498
  • DOI: 10.1038/s10038-019-0575-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Remarks] 研究室ホームページ(理化学研究所)
  • URL: http://www.riken.jp/lab-www/OA-team/index.html
• [Remarks] 研究室ホームページ(理化学研究所研究室紹介）
  • URL: https://www.riken.jp/research/labs/ims/bone_joint_dis/