Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

Ikuyo Kou, Yohei Takahashi, Todd A. Johnson, Atsushi Takahashi, Long Guo, Jin Dai, Xusheng Qiu, Swarkar Sharma, Aki Takimoto, Yoji Ogura, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya HosonoTaichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Douglas Londono, Derek Gordon, John A. Herring, Kota Watanabe, Kazuhiro Chiba, Naoyuki Kamatani, Qing Jiang, Yuji Hiraki, Michiaki Kubo, Yoshiaki Toyama, Tatsuhiko Tsunoda, Carol A. Wise, Yong Qiu, Chisa Shukunami, Morio Matsumoto, Shiro Ikegawa

Research output: Contribution to journalArticlepeer-review

194 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)676-679
Number of pages4
JournalNature Genetics
Issue number6
Publication statusPublished - 06-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics


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