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

Yoji Ogura, Kazuki Takeda, Ikuyo Kou, Anas Khanshour, Anna Grauers, Hang Zhou, Gang Liu, Yan-Hui Fan, Taifeng Zhou, Zhihong Wu, Yohei Takahashi, Morio Matsumoto, Elisabet Einarsdottir, Juha Kere, Dongsheng Huang, Guixing Qiu, Leilei Xu, Yong Qiu, Carol A Wise, You-Qiang Song, Nan Wu, Peiqiang Su, Paul Gerdhem, Kota Watanabe, Shiro Ikegawa

Journal: Scientific reports 2019;8(1):4730

PMID: 29549362

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 (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.

Address: 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.; Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.; 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.; Department of Spine Surgery, The Sun Yat-Sen Memorial 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.; 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 Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.; 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.; Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden.; Department of Orthopaedics, Karolinska University Hospital, Huddinge, Sweden.; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. [email protected].; Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan. [email protected].
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