An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis

Yoji Ogura, Kazuki Takeda, Ikuyo Kou, Anas Khanshour, Anna Grauers, Hang Zhou, Gang Liu, Yan Hui Fan, Taifeng Zhou, Zhihong Wu, Yohei Takahashi, Morio Matsumoto, Noriaki Kawakami, Taichi Tsuji, Koki Uno, Teppei Suzuki, Manabu Ito, Shohei Minami, Toshiaki Kotani, Tsuyoshi SakumaHaruhisa Yanagida, Hiroshi Taneichi, Ikuho Yonezawa, Hideki Sudo, Kazuhiro Chiba, Naobumi Hosogane, Kotaro Nishida, Kenichiro Kakutani, Tsutomu Akazawa, Takashi Kaito, Kei Watanabe, Katsumi Harimaya, Yuki Taniguchi, Hideki Shigematsu, Satoru Demura, Takahiro Iida, Katsuki Kono, Eijiro Okada, Nobuyuki Fujita, Mitsuru Yagi, Masaya Nakamura, Lori A. Karol, Karl E. Rathjen, Daniel J. Sucato, John G. Birch, Charles E. Johnston, Benjamin S. Richards, Brandon Ramo, Amy L. McIntosh, John A. Herring, Todd A. Milbrandt, Vishwas R. Talwakar, Henry J. Iwinski, Ryan D. Muchow, J. Channing Tassone, X. C. Liu, Richard Shindell, William Schrader, Craig Eberson, Anthony Lapinsky, Randall Loder, Joseph Davey, Elisabet Einarsdottir, Juha Kere, Dongsheng Huang, Guixing Qiu, Leilei Xu, Yong Qiu, Carol A. Wise, You Qiang Song, Nan Wu, Peiqiang Su, Paul Gerdhem, Kota Watanabe, Shiro Ikegawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

Original languageEnglish (US)
Article number4730
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Scoliosis
Meta-Analysis
Genome-Wide Association Study
Computer Simulation
Population
Chromosomes
Odds Ratio
Confidence Intervals
Genes

ASJC Scopus subject areas

  • General

Cite this

Ogura, Y., Takeda, K., Kou, I., Khanshour, A., Grauers, A., Zhou, H., ... Ikegawa, S. (2018). An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis. Scientific Reports, 8(1), [4730]. https://doi.org/10.1038/s41598-018-22552-x

An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis. / Ogura, Yoji; Takeda, Kazuki; Kou, Ikuyo; Khanshour, Anas; Grauers, Anna; Zhou, Hang; Liu, Gang; Fan, Yan Hui; Zhou, Taifeng; Wu, Zhihong; Takahashi, Yohei; Matsumoto, Morio; Kawakami, Noriaki; Tsuji, Taichi; Uno, Koki; Suzuki, Teppei; Ito, Manabu; Minami, Shohei; Kotani, Toshiaki; Sakuma, Tsuyoshi; Yanagida, Haruhisa; Taneichi, Hiroshi; Yonezawa, Ikuho; Sudo, Hideki; Chiba, Kazuhiro; Hosogane, Naobumi; Nishida, Kotaro; Kakutani, Kenichiro; Akazawa, Tsutomu; Kaito, Takashi; Watanabe, Kei; Harimaya, Katsumi; Taniguchi, Yuki; Shigematsu, Hideki; Demura, Satoru; Iida, Takahiro; Kono, Katsuki; Okada, Eijiro; Fujita, Nobuyuki; Yagi, Mitsuru; Nakamura, Masaya; Karol, Lori A.; Rathjen, Karl E.; Sucato, Daniel J.; Birch, John G.; Johnston, Charles E.; Richards, Benjamin S.; Ramo, Brandon; McIntosh, Amy L.; Herring, John A.; Milbrandt, Todd A.; Talwakar, Vishwas R.; Iwinski, Henry J.; Muchow, Ryan D.; Tassone, J. Channing; Liu, X. C.; Shindell, Richard; Schrader, William; Eberson, Craig; Lapinsky, Anthony; Loder, Randall; Davey, Joseph; Einarsdottir, Elisabet; Kere, Juha; Huang, Dongsheng; Qiu, Guixing; Xu, Leilei; Qiu, Yong; Wise, Carol A.; Song, You Qiang; Wu, Nan; Su, Peiqiang; Gerdhem, Paul; Watanabe, Kota; Ikegawa, Shiro.

In: Scientific Reports, Vol. 8, No. 1, 4730, 01.12.2018.

Research output: Contribution to journalArticle

Ogura, Y, Takeda, K, Kou, I, Khanshour, A, Grauers, A, Zhou, H, Liu, G, Fan, YH, Zhou, T, Wu, Z, Takahashi, Y, Matsumoto, M, Kawakami, N, Tsuji, T, Uno, K, Suzuki, T, Ito, M, Minami, S, Kotani, T, Sakuma, T, Yanagida, H, Taneichi, H, Yonezawa, I, Sudo, H, Chiba, K, Hosogane, N, Nishida, K, Kakutani, K, Akazawa, T, Kaito, T, Watanabe, K, Harimaya, K, Taniguchi, Y, Shigematsu, H, Demura, S, Iida, T, Kono, K, Okada, E, Fujita, N, Yagi, M, Nakamura, M, Karol, LA, Rathjen, KE, Sucato, DJ, Birch, JG, Johnston, CE, Richards, BS, Ramo, B, McIntosh, AL, Herring, JA, Milbrandt, TA, Talwakar, VR, Iwinski, HJ, Muchow, RD, Tassone, JC, Liu, XC, Shindell, R, Schrader, W, Eberson, C, Lapinsky, A, Loder, R, Davey, J, Einarsdottir, E, Kere, J, Huang, D, Qiu, G, Xu, L, Qiu, Y, Wise, CA, Song, YQ, Wu, N, Su, P, Gerdhem, P, Watanabe, K & Ikegawa, S 2018, 'An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis', Scientific Reports, vol. 8, no. 1, 4730. https://doi.org/10.1038/s41598-018-22552-x
Ogura, Yoji ; Takeda, Kazuki ; Kou, Ikuyo ; Khanshour, Anas ; Grauers, Anna ; Zhou, Hang ; Liu, Gang ; Fan, Yan Hui ; Zhou, Taifeng ; Wu, Zhihong ; Takahashi, Yohei ; Matsumoto, Morio ; Kawakami, Noriaki ; Tsuji, Taichi ; Uno, Koki ; Suzuki, Teppei ; Ito, Manabu ; Minami, Shohei ; Kotani, Toshiaki ; Sakuma, Tsuyoshi ; Yanagida, Haruhisa ; Taneichi, Hiroshi ; Yonezawa, Ikuho ; Sudo, Hideki ; Chiba, Kazuhiro ; Hosogane, Naobumi ; Nishida, Kotaro ; Kakutani, Kenichiro ; Akazawa, Tsutomu ; Kaito, Takashi ; Watanabe, Kei ; Harimaya, Katsumi ; Taniguchi, Yuki ; Shigematsu, Hideki ; Demura, Satoru ; Iida, Takahiro ; Kono, Katsuki ; Okada, Eijiro ; Fujita, Nobuyuki ; Yagi, Mitsuru ; Nakamura, Masaya ; Karol, Lori A. ; Rathjen, Karl E. ; Sucato, Daniel J. ; Birch, John G. ; Johnston, Charles E. ; Richards, Benjamin S. ; Ramo, Brandon ; McIntosh, Amy L. ; Herring, John A. ; Milbrandt, Todd A. ; Talwakar, Vishwas R. ; Iwinski, Henry J. ; Muchow, Ryan D. ; Tassone, J. Channing ; Liu, X. C. ; Shindell, Richard ; Schrader, William ; Eberson, Craig ; Lapinsky, Anthony ; Loder, Randall ; Davey, Joseph ; Einarsdottir, Elisabet ; Kere, Juha ; Huang, Dongsheng ; Qiu, Guixing ; Xu, Leilei ; Qiu, Yong ; Wise, Carol A. ; Song, You Qiang ; Wu, Nan ; Su, Peiqiang ; Gerdhem, Paul ; Watanabe, Kota ; Ikegawa, Shiro. / An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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abstract = "Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3{\%}. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95{\%} confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.",
author = "Yoji Ogura and Kazuki Takeda and Ikuyo Kou and Anas Khanshour and Anna Grauers and Hang Zhou and Gang Liu and Fan, {Yan Hui} and Taifeng Zhou and Zhihong Wu and Yohei Takahashi and Morio Matsumoto and Noriaki Kawakami and Taichi Tsuji and Koki Uno and Teppei Suzuki and Manabu Ito and Shohei Minami and Toshiaki Kotani and Tsuyoshi Sakuma and Haruhisa Yanagida and Hiroshi Taneichi and Ikuho Yonezawa and Hideki Sudo and Kazuhiro Chiba and Naobumi Hosogane and Kotaro Nishida and Kenichiro Kakutani and Tsutomu Akazawa and Takashi Kaito and Kei Watanabe and Katsumi Harimaya and Yuki Taniguchi and Hideki Shigematsu and Satoru Demura and Takahiro Iida and Katsuki Kono and Eijiro Okada and Nobuyuki Fujita and Mitsuru Yagi and Masaya Nakamura and Karol, {Lori A.} and Rathjen, {Karl E.} and Sucato, {Daniel J.} and Birch, {John G.} and Johnston, {Charles E.} and Richards, {Benjamin S.} and Brandon Ramo and McIntosh, {Amy L.} and Herring, {John A.} and Milbrandt, {Todd A.} and Talwakar, {Vishwas R.} and Iwinski, {Henry J.} and Muchow, {Ryan D.} and Tassone, {J. Channing} and Liu, {X. C.} and Richard Shindell and William Schrader and Craig Eberson and Anthony Lapinsky and Randall Loder and Joseph Davey and Elisabet Einarsdottir and Juha Kere and Dongsheng Huang and Guixing Qiu and Leilei Xu and Yong Qiu and Wise, {Carol A.} and Song, {You Qiang} and Nan Wu and Peiqiang Su and Paul Gerdhem and Kota Watanabe and Shiro Ikegawa",
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T1 - An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis

AU - Ogura, Yoji

AU - Takeda, Kazuki

AU - Kou, Ikuyo

AU - Khanshour, Anas

AU - Grauers, Anna

AU - Zhou, Hang

AU - Liu, Gang

AU - Fan, Yan Hui

AU - Zhou, Taifeng

AU - Wu, Zhihong

AU - Takahashi, Yohei

AU - Matsumoto, Morio

AU - Kawakami, Noriaki

AU - Tsuji, Taichi

AU - Uno, Koki

AU - Suzuki, Teppei

AU - Ito, Manabu

AU - Minami, Shohei

AU - Kotani, Toshiaki

AU - Sakuma, Tsuyoshi

AU - Yanagida, Haruhisa

AU - Taneichi, Hiroshi

AU - Yonezawa, Ikuho

AU - Sudo, Hideki

AU - Chiba, Kazuhiro

AU - Hosogane, Naobumi

AU - Nishida, Kotaro

AU - Kakutani, Kenichiro

AU - Akazawa, Tsutomu

AU - Kaito, Takashi

AU - Watanabe, Kei

AU - Harimaya, Katsumi

AU - Taniguchi, Yuki

AU - Shigematsu, Hideki

AU - Demura, Satoru

AU - Iida, Takahiro

AU - Kono, Katsuki

AU - Okada, Eijiro

AU - Fujita, Nobuyuki

AU - Yagi, Mitsuru

AU - Nakamura, Masaya

AU - Karol, Lori A.

AU - Rathjen, Karl E.

AU - Sucato, Daniel J.

AU - Birch, John G.

AU - Johnston, Charles E.

AU - Richards, Benjamin S.

AU - Ramo, Brandon

AU - McIntosh, Amy L.

AU - Herring, John A.

AU - Milbrandt, Todd A.

AU - Talwakar, Vishwas R.

AU - Iwinski, Henry J.

AU - Muchow, Ryan D.

AU - Tassone, J. Channing

AU - Liu, X. C.

AU - Shindell, Richard

AU - Schrader, William

AU - Eberson, Craig

AU - Lapinsky, Anthony

AU - Loder, Randall

AU - Davey, Joseph

AU - Einarsdottir, Elisabet

AU - Kere, Juha

AU - Huang, Dongsheng

AU - Qiu, Guixing

AU - Xu, Leilei

AU - Qiu, Yong

AU - Wise, Carol A.

AU - Song, You Qiang

AU - Wu, Nan

AU - Su, Peiqiang

AU - Gerdhem, Paul

AU - Watanabe, Kota

AU - Ikegawa, Shiro

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

AB - Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-Analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.

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