Abstract

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.

Details

Title
An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
Author
Ogura, Yoji 1 ; Takeda, Kazuki 1 ; Kou, Ikuyo 2 ; Khanshour, Anas 3 ; Grauers, Anna 4 ; Zhou, Hang 5 ; Liu, Gang 6   VIAFID ORCID Logo  ; Yan-Hui, Fan 7   VIAFID ORCID Logo  ; Zhou, Taifeng 5 ; Wu, Zhihong 8 ; Takahashi, Yohei 1 ; Matsumoto, Morio 9 ; Kawakami, Noriaki 10 ; Tsuji, Taichi 10 ; Uno, Koki 11 ; Suzuki, Teppei 11 ; Ito, Manabu 12 ; Minami, Shohei 13 ; Kotani, Toshiaki 13 ; Sakuma, Tsuyoshi 13 ; Yanagida, Haruhisa 14 ; Taneichi, Hiroshi 15 ; Yonezawa, Ikuho 16 ; Sudo, Hideki 17 ; Chiba, Kazuhiro 18 ; Hosogane, Naobumi 18 ; Nishida, Kotaro 19 ; Kakutani, Kenichiro 19 ; Akazawa, Tsutomu 20 ; Kaito, Takashi 21 ; Watanabe, Kei 22 ; Harimaya, Katsumi 23 ; Taniguchi, Yuki 24 ; Shigematsu, Hideki 25 ; Demura, Satoru 26 ; Iida, Takahiro 27 ; Kono, Katsuki 28 ; Okada, Eijiro 9 ; Fujita, Nobuyuki 9 ; Yagi, Mitsuru 9 ; Nakamura, Masaya 9 ; Karol, Lori A 29 ; Rathjen, Karl E 29 ; Sucato, Daniel J 29 ; Birch, John G 29 ; Johnston, Charles E 29 ; Richards, Benjamin S 29 ; Ramo, Brandon 29 ; McIntosh, Amy L 29 ; Herring, John A 29 ; Milbrandt, Todd A 30 ; Talwakar, Vishwas R 30 ; Iwinski, Henry J 30 ; Muchow, Ryan D 30 ; J Channing Tassone 31 ; X -C Liu 31 ; Shindell, Richard 32 ; Schrader, William 33 ; Eberson, Craig 34 ; Lapinsky, Anthony 35 ; Loder, Randall 36 ; Davey, Joseph 37 ; Einarsdottir, Elisabet 38   VIAFID ORCID Logo  ; Kere, Juha 39   VIAFID ORCID Logo  ; Huang, Dongsheng 40 ; Qiu, Guixing 41 ; Xu, Leilei 42 ; Qiu, Yong 42 ; Wise, Carol A 43 ; You-Qiang, Song 7 ; Wu, Nan 41 ; Su, Peiqiang 5 ; Gerdhem, Paul 44 ; Watanabe, Kota 9 ; Ikegawa, Shiro 2 

 Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan 
 Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan 
 Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA 
 Department of Orthopaedics, Sundsvall and Härnösand County Hospital, Sundsvall, Sweden; Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden 
 Department of Orthopaedic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 
 Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China 
 Department of Biochemistry, University of Hong Kong, Hong Kong, China 
 Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China; Medical Research Center of Orthopedics, Chinese Academy of Medical Sciences, Beijing, China 
 Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan 
10  Department of Orthopaedic Surgery, Meijo Hospital, Nagoya, Japan 
11  Department of Orthopaedic Surgery, National Hospital Organization, Kobe Medical Center, Kobe, Japan 
12  Department of Orthopaedic Surgery, National Hospital Organization, Hokkaido Medical Center, Sapporo, Japan 
13  Department of Orthopaedic Surgery, Seirei Sakura Citizen Hospital, Sakura, Japan 
14  Department of Orthopaedic Surgery, Fukuoka Children’s Hospital, Fukuoka, Japan 
15  Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan 
16  Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo, Japan 
17  Department of Advanced Medicine for Spine and Spinal Cord Disorders, Hokkaido University Graduate School of Medicine, Sapporo, Japan 
18  Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan 
19  Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan 
20  Department of Orthopaedic Surgery, St. Marianna University School of Medicine, Kawasaki, Japan 
21  Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan 
22  Department of Orthopaedic Surgery, Niigata University Hospital, Niigata, Japan 
23  Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 
24  Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan 
25  Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan 
26  Department of Orthopaedic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan 
27  Department of Orthopaedic Surgery, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan 
28  Department of Orthopaedic Surgery, Kono Othopaedic Clinic, Tokyo, Japan 
29  Department of Orthopaedic Surgery, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA 
30  Department of Orthopaedic Surgery, Shriners Hospitals for Children, Lexington, Kentucky, USA 
31  Department of Orthopaedic Surgery, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin, USA 
32  OrthoArizona, Phoenix, Arizona, USA 
33  Departments of Orthopedics, Sports Medicine, and Surgical Services, Akron Children’s Hospital, Akron, Ohio, USA 
34  Pediatric Orthopaedics and Scoliosis, Hasbro Children’s Hospital, Providence, Rhode Island, USA 
35  University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, USA 
36  Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA 
37  University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 
38  Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden 
39  Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, United Kingdom 
40  Department of Spine Surgery, The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China 
41  Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China; Medical Research Center of Orthopedics, Chinese Academy of Medical Sciences, Beijing, China 
42  Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China 
43  Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA; 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 
44  Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden; Department of Orthopaedics, Karolinska University Hospital, Huddinge, Sweden 
Pages
1-7
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2014498512
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.