Establishment of predictive models for the onset and progression for adolescent idiopathic scoliosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03787
• 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: Keio University
• Principal Investigator: MATSUMOTO Morio 慶應義塾大学, 医学部(信濃町), 教授 (40209656)
• Co-Investigator(Kenkyū-buntansha): 渡邉 航太 慶應義塾大学, 医学部(信濃町), 准教授 (60317170) ; 寺尾 知可史 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, チームリーダー (60610459)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 思春期特発性側弯症 / 発症 / 進行 / 予測 / Polygenic risk score / 全ゲノム関連解析

Outline of Final Research Achievements

We have identified three disease susceptibility genes and two genes involved in the onset and progression of adolescent idiopathic scoliosis (scoliosis), respectively, by genome-wide association analysis (GWAS). However, the AUC of the prediction model created with these genes was only 0.6. In this study, GWAS was performed on an additional 4,000 samples, and a total of 14 new loci associated with disease onset, as well as disease susceptibility genes, were identified. In addition, the Polygenic risk score (PRS) method was used, and the value of BMI was also incorporated as an explanatory variable in the model, resulting in an AUROC of 0.71. The AUROC of the PRS for severe disease was 0.69, indicating reasonable results.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

本研究では合計６０００人分の検体のGWASの結果を行い、Polygenic risk score(PRS)という手法を用い、さらにBMIの値を説明変数として組み込み、側弯症の発症と進行予測モデルを世界で初めて作成した。このことは発症の原因や進行の原因が明らかになっていない側弯症診療の予後予測の一方を踏み出したという点で、非常に大きな意義がある。一方、発症のAUROCは0.71、重症化のAUROCは0.69であり、臨床応用するには精度が足りないことも課題として示された。今後は遺伝子情報だけでなく臨床的な指標をモデルに取り込むことで更に精度を上げる必要がある。