Predictive Model for Onset and Progression of Adolescent Idiopathic Scoliosis

• Project/Area Number: 24390357
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: MATSUMOTO Morio 慶應義塾大学, 医学部, 教授 (40209656)
• Co-Investigator(Kenkyū-buntansha): WATANABE Kota 慶應義塾大学, 医学部, 講師 (60317170) ; HOSOGANE Naobumi 防衛医科大学校, 病院整形外科, 助教 (10365306) ; 高橋 洋平 慶應義塾大学, 医学部, 助教 (00445305)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 特発性側弯症 / 遺伝子 / 進行予測 / 環境因子 / 思春期特発性側弯症 / 進行予測モデル

Outline of Final Research Achievements

This study was conducted to develop a predictive model for onset and progression of adolescent idiopathic scoliosis.During the study period, we collected approximately 3500 DNA samples.Using genome-wide association study,approximately 550 thousands of SNPs were investigated and we found 4 single nucleotide polimorphisms(SNP) that were related to the onset of scoliosis and 2 SNPs related to the progression of the curve. The 4 SNPS related to the onset of scoliosis were located closely to genes, LBX1, GPR 126, PAX1 and gene X. The 2 SNPs related to the progression of the curve were located closely to SOX9, KCNJ2, and Gene X. Using these genes, predictive models for the onset and progression of adolescent idiopathic scoliosis can be developed.

Research Products

• [Journal Article] A PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females (2015)
  • Author(s): 27) Swarkar Sharma, Douglas Londono, Walter Eckalbar, Xiaochong Gao, Dongping Zhang, Kristen Mauldin, Ikuyo Kou, Atsushi Takahashi, Morio Matsumoto, Nobuhiro Kamiya, Karl Murphy, Reuel Cornelia, John Herring, Dennis Burns, Nadav Ahituv, Shiro Ikegawa, Derek Gordon, Carol Wise
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6452-6452
  • DOI: 10.1038/ncomms7452
  • Peer Reviewed / Open Access
• [Journal Article] A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups (2014)
  • Author(s): Londono D, Kou I, Johnson TA, Sharma S, Ogura Y, Tsunoda T, Takahashi A, Matsumoto M, Herring JA, Lam TP, Wang X, Tam EMS, Song YQ, Fan YH, Chan D, Cheah KSE, Qiu X, Jiang H, Huang D, ,Su P, Sham P, Cheung KMC, Luk KDK, Gordon1 D, Qiu Y, Cheng J, Tang N, Ikegawa S, Wise CA
  • Journal Title: ournal of Medical Genetics Volume: 51 Issue: 6 Pages: 401-406
  • DOI: 10.1136/jmedgenet-2013-102067
  • Peer Reviewed
• [Journal Article] 最新基礎科学/知っておきたい 思春期特発性側彎症発症に関する新たな遺伝子GPR126 (2014)
  • Author(s): 高橋洋平, 黄 郁代, 松本守雄, 池川志郎
  • Journal Title: 臨床整形外科 Volume: 49
• [Journal Article] 思春期特発性側弯症の全ゲノム相関解析 (2014)
  • Author(s): 松本守雄, 高橋洋平, 小倉洋二, 渡辺航太, 戸山芳昭
  • Journal Title: 整形・災害外科 Volume: 57 Pages: 295-299
• [Journal Article] Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. (2013)
  • Author(s): Kou I, Matsumoto M, Ikegawa S et al.
  • Journal Title: Nature Genetics Volume: 45: Issue: 6 Pages: 676-679
  • DOI: 10.1038/ng.2639
  • Peer Reviewed
• [Journal Article] Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3 (2013)
  • Author(s): Miyake A, Kou I, Takahashi Y, Johnson TA, Ogura Y, Dai J, Qiu X, Takahashi A, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Kubo M, Tsunoda T, Watanabe K, Chiba K, Toyama Y, Qiu Y, Matsumoto M (co-corresponding), Ikegawa S
  • Journal Title: PLoS One Volume: 8 Issue: 9 Pages: e72802-e72802
  • DOI: 10.1371/journal.pone.0072802
  • Peer Reviewed
• [Journal Article] A replication study for association of 53 single nucleotide polymorphisms in a scoliosis prognostic test with progression of adolescent idiopathic scoliosis in Japanese. (2013)
  • Author(s): Ogura Y, Takahashi Y, Kou I, Nakajima M, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Yonezawa I, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Toyama Y, Matsumoto M, Ikegawa S
  • Journal Title: Spine Volume: 38 Issue: 16 Pages: 1375-1379
  • DOI: 10.1097/brs.0b013e3182947d21
  • Peer Reviewed
• [Journal Article] A replication study for association of five single nucleotide polymorphisms with curve progression of adolescent idiopathic scoliosis in Japanese patients (2013)
  • Author(s): Ogura Y, Takahashi Y, Kou I, Nakajima M, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Yonezawa I, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Toyama Y, Matsumoto M, Ikegawa S
  • Journal Title: Spine Volume: 38 Issue: 7 Pages: 571-575
  • DOI: 10.1097/brs.0b013e3182761535
  • Peer Reviewed
• [Journal Article] A Replication Study for Association of Five Single Nucleotide Polymorphisms With Curve Progression of Adolescent Idiopathic Scoliosis in Japanese. (2013)
  • Author(s): Takahashi Y(2番目), Matsumoto M(20番目), Watanabe K (18番目)以下18名.
  • Journal Title: Spine Volume: 38 Issue: 7 Pages: 571-575
  • DOI: 10.1097/brs.0b013e31827c99f0
  • Peer Reviewed
• [Presentation] 思春期特発性側弯症の原因遺伝子 -遺伝子診断の現況 (2014)
  • Author(s): 高橋洋平, 小倉洋二, 黄郁代, 高橋弘, 河野克己, 川上紀明, 辻太一, 宇野耕吉, 鈴木哲平, 伊東学, 須藤英毅, 南昌平, 小谷俊明, 柳田晴久, 種市洋, 米澤郁穂, 渡辺航太, 戸山芳昭, 松本守雄, 池川志郎
  • Organizer: 第48回日本側弯症学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2014-10-30 – 2014-11-01
• [Presentation] 思春期特発性側彎症の全ゲノム相関解析―発症・進行予測への応用を目指して― (2014)
  • Author(s): 松本守雄, 高橋洋平, 小倉洋二, 三宅 敦, 渡辺航太, 戸山芳昭, 池川志郎
  • Organizer: 第29回日本整形外科基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] 思春期特発性側弯症の大規模ゲノムワイド相関解析：新規の座位の同定 (2014)
  • Author(s): 795)小倉洋二, 松本守雄, 黄 郁代, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊藤 学, 南 昌平, 米澤郁穂, 辻 太一, 鈴木哲平, 須藤英毅, 渡辺航太, 戸山芳昭, 池川志郎
  • Organizer: 第29回日本整形外科基礎学術集会 2014.10.9-10
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] A genome-wide association study identified a novel susceptibility locus for severe adolescent isiopathic scoliosis (2014)
  • Author(s): 287)Miyake A, Matsumoto M, Takahashi Y, Ogura Y, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Watanabe K, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Chiba K, Toyama Y, Ikegawa S
  • Organizer: Scoliosis Research Society 49th Annual Meeting & Course
  • Place of Presentation: Anchorage
  • Year and Date: 2014-09-10 – 2014-09-13
• [Presentation] rs11190870 is not associated with severity of adolescent idiopathic scoliosis in Japanese. (2014)
  • Author(s): 281)Takahashi Y , Inaba I, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Yonezawa I, Ogura Y, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Toyama Y, Matsumoto M, Ikegawa S
  • Organizer: 10th Meeting of the International Research Society of Spinal Deformities
  • Place of Presentation: Sapporo
  • Year and Date: 2014-06-29 – 2014-07-02
• [Presentation] 思春期特発性側弯症のゲノムワイド相関解析. 側弯の発症に関与する遺伝子の解析 (2014)
  • Author(s): 小倉洋二, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 渡辺航太, 戸山芳昭, 松本守雄, 辻太一, 鈴木哲平, 須藤英毅, 高橋洋平, 南昌平, 小谷俊明, 柳田晴久, 米澤郁穂, 細金直文, 種市洋, 千葉一裕, 岡田英次朗, 池川志郎:
  • Organizer: 第43回日本脊椎脊髄病学会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-17 – 2014-04-19
• [Presentation] A genome-wide association study identifying a new susceptibility locus for adolescent idiopathic scoliosis. (2013)
  • Author(s): akahashi Y, Matsumoto M, Kono K, Kawakami N, Ito M, Uno K, Minami S, Yanagida H, Taneichi H, Watanabe K, Toyama Y, Ikegawa S
  • Organizer: 50th Anniversary International Phillip Zorab Symposium
  • Place of Presentation: UK,London
• [Presentation] 思春期特発性側弯症の進行に関する遺伝子マーカーの検討：日本人での大規模再現解析 (2013)
  • Author(s): 小倉洋二, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 米澤郁穂, 種市洋, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 渡辺航太, 戸山芳昭, 千葉一裕, 松本守雄, 池川志郎
  • Organizer: 第42回日本脊椎脊髄病学会
  • Place of Presentation: 沖縄
• [Presentation] 思春期特発性側弯症胸椎メインカーブ例の全ゲノム相関解析. (2013)
  • Author(s): 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 種市洋, 米澤郁穂, 渡辺航太, 辻太一, 鈴木哲平, 須藤英毅, 戸山芳昭, 池川志郎, 松本守雄
  • Organizer: 第42回日本脊椎脊髄病学会
  • Place of Presentation: 沖縄
• [Presentation] 思春期特発性側弯症の全ゲノム相関解析. (2013)
  • Author(s): 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 柳田晴久, 種市洋, 米澤郁穂, 戸山芳昭, 池川志郎, 松本守雄
  • Organizer: 第86回日本整形外科学会学術総会
  • Place of Presentation: 広島
• [Presentation] 思春期特発性側彎症の進行に関する一塩基多型の検討 日本人での大規模再現解析. (2013)
  • Author(s): 小倉 洋二, 高橋 洋平, 黄 郁代, 河野 克己, 川上 紀明, 宇野 耕吉, 伊東 学, 南 昌平, 柳田 晴久, 種市 洋, 米澤 郁穂, 渡邉 航太, 戸山 芳昭, 松本 守雄, 池川 志郎
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
• [Presentation] 思春期特発性側弯症のゲノムワイド相関解析：発症に関与する遺伝子の解析 (2013)
  • Author(s): 小倉洋二, 黄郁代, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平, 米澤郁穂, 柳田晴久, 種市洋, 宿南知佐, 渡辺航太, 辻太一, 鈴木哲平, 須藤英毅, 小谷俊明, 千葉一裕, 戸山芳昭, 松本守雄, 池川志郎
  • Organizer: 第47回日本側弯症学会
  • Place of Presentation: 高知
• [Presentation] 思春期特発性側弯症のゲノムワイド相関解析：側弯の進行に関与する遺伝子の解析 (2013)
  • Author(s): 小倉洋二, 高橋洋平, 河野克己, 川上紀明, 宇野耕吉, 伊東学, 南昌平,
  • Organizer: 第47回日本側弯症学会
  • Place of Presentation: 高知
• [Presentation] Biomarker and Genes Related to Scoliosis. (2012)
  • Author(s): Morio Matsumoto
  • Organizer: Basic Research Meeting of Korean Neurosurgery
  • Place of Presentation: Incheon(招待講演)
  • Year and Date: 2012-05-25
• [Presentation] Genome-wide association study in adolescent idiopathic scoliosis. (2012)
  • Author(s): Takahashi y Matsumoto M, 以下15名
  • Organizer: Eurospine 2012
  • Place of Presentation: Amsterdam
• [Presentation] Genome-Wide Association Study Identified a New Susceptibility Locus for Adolescent Idiopathic Scoliosis. (2012)
  • Author(s): Takahashi Y, Matsumoto M, 以下13名
  • Organizer: SRS 47th Annual Meeting & Course
  • Place of Presentation: Chicago
• [Presentation] 思春期特発性側弯症の疾患感受性多型rslll90870の重症度との相関. (2012)
  • Author(s): 高橋洋平、松本守雄(12番目)以下10名
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
• [Book] 側弯症治療の最前線 (2013)
  • Author(s): 高橋洋平、松本守雄,池川志郎
  • Total Pages: 323
  • Publisher: 医薬ジャーナル社