title: Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis.
abstract: Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
authors.forename: Ikuyo
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authors.lastname: Kou
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authors.lastname: Takahashi
authors.forename: Todd A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Atsushi
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authors.forename: Long
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authors.forename: Shohei
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authors.lastname: Minami
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authors.lastname: Yanagida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Taneichi
authors.forename: Naoya
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authors.lastname: Hosono
authors.forename: Taichi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Teppei
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Sudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kotani
authors.forename: Ikuho
authors.initials: I
authors.lastname: Yonezawa
authors.forename: Douglas
authors.initials: D
authors.lastname: Londono
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: John A
authors.initials: JA
authors.lastname: Herring
authors.forename: Kota
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiraki
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wise
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Chisa
authors.initials: C
authors.lastname: Shukunami
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shiro
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authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000818:Animals; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012600:Scoliosis
chemical_list: C488660:ADGRG6 protein, human; D043562:Receptors, G-Protein-Coupled