Abstract

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10−20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

Details

Title
A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis
Author
Kou, Ikuyo 1 ; Watanabe, Kota 2 ; Takahashi, Yohei 3 ; Momozawa, Yukihide 4 ; Khanshour, Anas 5 ; Grauers, Anna 6 ; Zhou, Hang 7 ; Liu, Gang 8   VIAFID ORCID Logo  ; Yan-Hui, Fan 9   VIAFID ORCID Logo  ; Takeda, Kazuki 3 ; Ogura, Yoji 3 ; Zhou, Taifeng 7 ; Iwasaki, Yusuke 4 ; Kubo, Michiaki 4 ; Wu, Zhihong 10 ; Matsumoto, Morio 2 ; Kawakami, Noriaki 11 ; Uno, Koki 12 ; Suzuki, Teppei 12 ; Sudo, Hideki 13 ; Minami, Shohei 14 ; Kotani, Toshiaki 14 ; Ito, Manabu 15 ; Yanagida, Haruhisa 16 ; Taneichi, Hiroshi 17 ; Yonezawa, Ikuho 18 ; Chiba, Kazuhiro 19 ; Hosogane, Naobumi 19 ; Fujita, Nobuyuki 2 ; Yagi, Mitsuru 2 ; Kono, Katsuki 20 ; Okada, Eijiro 21 ; Nishida, Kotaro 22 ; Kakutani, Kenichiro 22 ; Sakuma, Tsuyoshi 14 ; Harimaya, Katsumi 23 ; Kaito, Takashi 24 ; Watanabe, Kei 25 ; Taniguchi, Yuki 26 ; Tsuji, Taichi 27 ; Akazawa, Tsutomu 28 ; 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 ; Einarsdottir, Elisabet 30   VIAFID ORCID Logo  ; Kere, Juha 31   VIAFID ORCID Logo  ; Huang, Dongsheng 32 ; Qiu, Guixing 33 ; Qiu, Yong 34 ; Wise, Carol A 35   VIAFID ORCID Logo  ; You-Qiang, Song 9 ; Wu, Nan 33   VIAFID ORCID Logo  ; Su, Peiqiang 7 ; Gerdhem, Paul 36 ; Ikegawa, Shiro 1 

1  Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan 
2  Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan 
3  Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan 
4  Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan 
5  Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA 
6  Department of Orthopaedics, Sundsvall and Härnösand County Hospital, Sundsvall, Sweden; Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden 
7  Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 
8  Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China 
9  Department of Biochemistry, University of Hong Kong, Hong Kong, China 
10  Department of Central Laboratory, 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 
11  Department of Orthopaedic Surgery, Meijo Hospital, Nagoya, Japan 
12  Department of Orthopaedic Surgery, National Hospital Organization, Kobe Medical Center, Kobe, Japan 
13  Department of Advanced Medicine for Spine and Spinal Cord Disorders, Hokkaido University Graduate School of Medicine, Sapporo, Japan 
14  Department of Orthopaedic Surgery, Seirei Sakura Citizen Hospital, Sakura, Japan 
15  Department of Orthopaedic Surgery, National Hospital Organization, Hokkaido Medical Center, Sapporo, Japan 
16  Department of Orthopaedic Surgery, Fukuoka Children’s Hospital, Fukuoka, Japan 
17  Department of Orthopaedic Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan 
18  Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo, Japan 
19  Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan 
20  Department of Orthopaedic Surgery, Kono Othopaedic Clinic, Tokyo, Japan 
21  Department of Orthopaedic Surgery, Saiseikai Central Hospital, Tokyo, Japan 
22  Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan 
23  Department of Orthopaedic Surgery, Kyushu University Beppu Hospital, Beppu, Japan 
24  Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, Suita, Japan 
25  Department of Orthopedic Surgery, Niigata University Medical and Dental Hospital, Niigata, Japan 
26  Department of Orthopedic Surgery, The University of Tokyo Hospital, Tokyo, Japan 
27  Department of Orthopaedic Surgery, Toyota Kosei Hospital, Toyota, Japan 
28  Department of Orthopaedic Surgery, St. Marianna University School of Medicine, Tokyo, Japan 
29  Department of Orthopaedic Surgery, Texas Scottish Rite Hospital for Children, Dallas, Texas, USA 
30  Folkhälsan Institute of Genetics, and Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition, , Karolinska Institutet, Huddinge, Sweden 
31  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, UK 
32  Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China 
33  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 
34  Department of Spine Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China 
35  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, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA; Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA; Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA 
36  Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, Stockholm, Sweden; Department of Orthopaedics, Karolinska University Hospital, Stockholm, Sweden 
Pages
1-8
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-29011-7
ProQuest document ID
2081526137
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.