Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3

Atsushi Miyake, Ikuyo Kou, Yohei Takahashi, Todd A. Johnson, Yoji Ogura, Jin Dai, Xusheng Qiu, Atsushi Takahashi, Hua Jiang, Huang Yan, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Haruhisa Yanagida, Hiroshi Taneichi, Naoya Hosono, Taichi Tsuji, Teppei Suzuki & 11 others Hideki Sudo, Toshiaki Kotani, Ikuho Yonezawa, Michiaki Kubo, Tatsuhiko Tsunoda, Kota Watanabe, Kazuhiro Chiba, Yoshiaki Toyama, Yong Qiu, Morio Matsumoto, Shiro Ikegawa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10 -8 , odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10 -12 , OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

Original languageEnglish
Article numbere72802
JournalPloS one
Volume8
Issue number9
DOIs
Publication statusPublished - 04-09-2013

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scoliosis
Scoliosis
Chromosomes
Genes
chromosomes
loci
Genome-Wide Association Study
odds ratio
etiology
Odds Ratio
Phenotype
phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Miyake, A., Kou, I., Takahashi, Y., Johnson, T. A., Ogura, Y., Dai, J., ... Ikegawa, S. (2013). Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3. PloS one, 8(9), [e72802]. https://doi.org/10.1371/journal.pone.0072802
Miyake, Atsushi ; Kou, Ikuyo ; Takahashi, Yohei ; Johnson, Todd A. ; Ogura, Yoji ; Dai, Jin ; Qiu, Xusheng ; Takahashi, Atsushi ; Jiang, Hua ; Yan, Huang ; Kono, Katsuki ; Kawakami, Noriaki ; Uno, Koki ; Ito, Manabu ; Minami, Shohei ; Yanagida, Haruhisa ; Taneichi, Hiroshi ; Hosono, Naoya ; Tsuji, Taichi ; Suzuki, Teppei ; Sudo, Hideki ; Kotani, Toshiaki ; Yonezawa, Ikuho ; Kubo, Michiaki ; Tsunoda, Tatsuhiko ; Watanabe, Kota ; Chiba, Kazuhiro ; Toyama, Yoshiaki ; Qiu, Yong ; Matsumoto, Morio ; Ikegawa, Shiro. / Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3. In: PloS one. 2013 ; Vol. 8, No. 9.
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abstract = "Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2{\%} of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10 -8 , odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10 -12 , OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.",
author = "Atsushi Miyake and Ikuyo Kou and Yohei Takahashi and Johnson, {Todd A.} and Yoji Ogura and Jin Dai and Xusheng Qiu and Atsushi Takahashi 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 Michiaki Kubo and Tatsuhiko Tsunoda and Kota Watanabe and Kazuhiro Chiba and Yoshiaki Toyama and Yong Qiu and Morio Matsumoto and Shiro Ikegawa",
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Miyake, A, Kou, I, Takahashi, Y, Johnson, TA, Ogura, Y, Dai, J, Qiu, X, Takahashi, A, 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, Kubo, M, Tsunoda, T, Watanabe, K, Chiba, K, Toyama, Y, Qiu, Y, Matsumoto, M & Ikegawa, S 2013, 'Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3', PloS one, vol. 8, no. 9, e72802. https://doi.org/10.1371/journal.pone.0072802

Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3. / Miyake, Atsushi; Kou, Ikuyo; Takahashi, Yohei; Johnson, Todd A.; Ogura, Yoji; Dai, Jin; Qiu, Xusheng; Takahashi, Atsushi; Jiang, Hua; Yan, Huang; Kono, Katsuki; Kawakami, Noriaki; Uno, Koki; Ito, Manabu; Minami, Shohei; Yanagida, Haruhisa; Taneichi, Hiroshi; Hosono, Naoya; Tsuji, Taichi; Suzuki, Teppei; Sudo, Hideki; Kotani, Toshiaki; Yonezawa, Ikuho; Kubo, Michiaki; Tsunoda, Tatsuhiko; Watanabe, Kota; Chiba, Kazuhiro; Toyama, Yoshiaki; Qiu, Yong; Matsumoto, Morio; Ikegawa, Shiro.

In: PloS one, Vol. 8, No. 9, e72802, 04.09.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3

AU - Miyake, Atsushi

AU - Kou, Ikuyo

AU - Takahashi, Yohei

AU - Johnson, Todd A.

AU - Ogura, Yoji

AU - Dai, Jin

AU - Qiu, Xusheng

AU - Takahashi, Atsushi

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 - Kubo, Michiaki

AU - Tsunoda, Tatsuhiko

AU - Watanabe, Kota

AU - Chiba, Kazuhiro

AU - Toyama, Yoshiaki

AU - Qiu, Yong

AU - Matsumoto, Morio

AU - Ikegawa, Shiro

PY - 2013/9/4

Y1 - 2013/9/4

N2 - Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10 -8 , odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10 -12 , OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

AB - Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P = 4.00×10 -8 , odds ratio [OR] = 2.05). Its association was replicated in a Chinese population (combined P = 6.43×10 -12 , OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

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U2 - 10.1371/journal.pone.0072802

DO - 10.1371/journal.pone.0072802

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