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 Hosono; Taichi 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

doi:10.1038/ng.2639

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

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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.

Original language	English (US)
Pages (from-to)	676-679
Number of pages	4
Journal	Nature genetics
Volume	45
Issue number	6
DOIs	https://doi.org/10.1038/ng.2639
State	Published - Jun 2013

ASJC Scopus subject areas

Genetics

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Kou, I., Takahashi, Y., Johnson, T. A., Takahashi, A., Guo, L., Dai, J., Qiu, X., Sharma, S., Takimoto, A., Ogura, Y., Jiang, H., Yan, H., Kono, K., Kawakami, N., Uno, K., Ito, M., Minami, S., Yanagida, H., Taneichi, H., ... Ikegawa, S. (2013). Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nature genetics, 45(6), 676-679. https://doi.org/10.1038/ng.2639

Kou, I, Takahashi, Y, Johnson, TA, Takahashi, A, Guo, L, Dai, J, Qiu, X, Sharma, S, Takimoto, A, Ogura, Y, Jiang, H, Yan, H, Kono, K, Kawakami, N, Uno, K, Ito, M, Minami, S, Yanagida, H, Taneichi, H, Hosono, N, Tsuji, T, Suzuki, T, Sudo, H, Kotani, T, Yonezawa, I, Londono, D, Gordon, D, Herring, JA, Watanabe, K, Chiba, K, Kamatani, N, Jiang, Q, Hiraki, Y, Kubo, M, Toyama, Y, Tsunoda, T, Wise, CA, Qiu, Y, Shukunami, C, Matsumoto, M & Ikegawa, S 2013, 'Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis', Nature genetics, vol. 45, no. 6, pp. 676-679. https://doi.org/10.1038/ng.2639

@article{21de68e2f9b94e419e5d36958ae78b9b,

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.",

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

note = "Funding Information: We thank all participating individuals with AIS and the doctors and staff of the collaborating institutes. We especially thank N. Suzuki, M. Saito, M. Kamata, N. Hosogane, E. Okada and H. Hase for their help in collecting samples. We also thank S. Tominaga and T. Isono for technical assistance. This work was supported by a grant-in-aid to M.M. from the Japanese Orthopaedic Association (JOA–Subsidized Science Project Research 2009-1) and by funding from the US National Institutes of Health (R01052973), the Crystal Charity Ball, the Scoliosis Research Society and the Texas Scottish Rite Hospital Research Fund to C.A.W.",

year = "2013",

month = jun,

doi = "10.1038/ng.2639",

language = "English (US)",

volume = "45",

pages = "676--679",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

AU - Kou, Ikuyo

AU - Takahashi, Yohei

AU - Johnson, Todd A.

AU - Takahashi, Atsushi

AU - Guo, Long

AU - Dai, Jin

AU - Qiu, Xusheng

AU - Sharma, Swarkar

AU - Takimoto, Aki

AU - Ogura, Yoji

AU - Jiang, Hua

AU - Yan, Huang

AU - Kono, Katsuki

AU - Kawakami, Noriaki

AU - Uno, Koki

AU - Ito, Manabu

AU - Minami, Shohei

AU - Yanagida, Haruhisa

AU - Taneichi, Hiroshi

AU - Hosono, Naoya

AU - Tsuji, Taichi

AU - Suzuki, Teppei

AU - Sudo, Hideki

AU - Kotani, Toshiaki

AU - Yonezawa, Ikuho

AU - Londono, Douglas

AU - Gordon, Derek

AU - Herring, John A.

AU - Watanabe, Kota

AU - Chiba, Kazuhiro

AU - Kamatani, Naoyuki

AU - Jiang, Qing

AU - Hiraki, Yuji

AU - Kubo, Michiaki

AU - Toyama, Yoshiaki

AU - Tsunoda, Tatsuhiko

AU - Wise, Carol A.

AU - Qiu, Yong

AU - Shukunami, Chisa

AU - Matsumoto, Morio

AU - Ikegawa, Shiro

N1 - Funding Information: We thank all participating individuals with AIS and the doctors and staff of the collaborating institutes. We especially thank N. Suzuki, M. Saito, M. Kamata, N. Hosogane, E. Okada and H. Hase for their help in collecting samples. We also thank S. Tominaga and T. Isono for technical assistance. This work was supported by a grant-in-aid to M.M. from the Japanese Orthopaedic Association (JOA–Subsidized Science Project Research 2009-1) and by funding from the US National Institutes of Health (R01052973), the Crystal Charity Ball, the Scoliosis Research Society and the Texas Scottish Rite Hospital Research Fund to C.A.W.

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.2639

DO - 10.1038/ng.2639

M3 - Article

C2 - 23666238

AN - SCOPUS:84878735692

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SP - 676

EP - 679

JO - Nature genetics

JF - Nature genetics

IS - 6

ER -

Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis

Abstract

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