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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis.

Sci Rep. 2018 Mar 16;8(1):4730
Yoji Ogura 1 , Kazuki Takeda 1 , Ikuyo Kou 2 , Anas Khanshour 3 , Anna Grauers 4 , Hang Zhou 5 , Gang Liu 6 , Yan-Hui Fan 7 , Taifeng Zhou 5 , Zhihong Wu 8 , Yohei Takahashi 1 , Morio Matsumoto 1 , Japan Scoliosis Clinical Research Group (JSCRG) , Texas Scottish Rite Hospital for Children Clinical Group (TSRHCCG) , Elisabet Einarsdottir 9 , Juha Kere 10 , Dongsheng Huang 11 , Guixing Qiu 8 , Leilei Xu 12 , Yong Qiu 12 , Carol A Wise 13 , You-Qiang Song 7 , Nan Wu 8 , Peiqiang Su 5 , Paul Gerdhem 14 , Kota Watanabe 15 , Shiro Ikegawa 16
Yoji Ogura 1 , Kazuki Takeda 1 , Ikuyo Kou 2 , Anas Khanshour 3 , Anna Grauers 4 , Hang Zhou 5 , Gang Liu 6 , Yan-Hui Fan 7 , Taifeng Zhou 5 , Zhihong Wu 8 , Yohei Takahashi 1 , Morio Matsumoto 1 , Japan Scoliosis Clinical Research Group (JSCRG) , Texas Scottish Rite Hospital for Children Clinical Group (TSRHCCG) , Elisabet Einarsdottir 9 , Juha Kere 10 , Dongsheng Huang 11 , Guixing Qiu 8 , Leilei Xu 12 , Yong Qiu 12 , Carol A Wise 13 , You-Qiang Song 7 , Nan Wu 8 , Peiqiang Su 5 , Paul Gerdhem 14 , Kota Watanabe 15 , Shiro Ikegawa 16
+ et al

[No authors listed]

Author information
  • 1 Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
  • 2 Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
  • 3 Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA.
  • 4 Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden.
  • 5 Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • 6 Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
  • 7 Department of Biochemistry, University of Hong Kong, Hong Kong, China.
  • 8 Medical Research Center of Orthopedics, Chinese Academy of Medical Sciences, Beijing, China.
  • 9 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
  • 10 Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, United Kingdom.
  • 11 Department of Spine Surgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China.
  • 12 Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 13 McDermott Center for Human Growth and Development, Department of Pediatrics and Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
  • 14 Department of Orthopaedics, Karolinska University Hospital, Huddinge, Sweden.
  • 15 Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. watakota@gmail.com.
  • 16 Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan. sikegawa@ims.u-tokyo.ac.jp.

摘要

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

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