Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

Ikuyo Kou; Nao Otomo; Kazuki Takeda; Yukihide Momozawa; Hsing Fang Lu; Michiaki Kubo; Yoichiro Kamatani; Yoji Ogura; Yohei Takahashi; Masahiro Nakajima; Shohei Minami; Koki Uno; Noriaki Kawakami; Manabu Ito; Ikuho Yonezawa; Kei Watanabe; Takashi Kaito; Haruhisa Yanagida; Hiroshi Taneichi; Katsumi Harimaya; Yuki Taniguchi; Hideki Shigematsu; Takahiro Iida; Satoru Demura; Ryo Sugawara; Nobuyuki Fujita; Mitsuru Yagi; Eijiro Okada; Naobumi Hosogane; Katsuki Kono; Masaya Nakamura; Kazuhiro Chiba; Toshiaki Kotani; Tsuyoshi Sakuma; Tsutomu Akazawa; Teppei Suzuki; Kotaro Nishida; Kenichiro Kakutani; Taichi Tsuji; Hideki Sudo; Akira Iwata; Tatsuya Sato; Satoshi Inami; Morio Matsumoto; Chikashi Terao; Kota Watanabe; Shiro Ikegawa

doi:10.1038/s41467-019-11596-w

Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

Ikuyo Kou, Nao Otomo, Kazuki Takeda, Yukihide Momozawa, Hsing Fang Lu, Michiaki Kubo, Yoichiro Kamatani, Yoji Ogura, Yohei Takahashi, Masahiro Nakajima, Shohei Minami, Koki Uno, Noriaki Kawakami, Manabu Ito, Ikuho Yonezawa, Kei Watanabe, Takashi Kaito, Haruhisa Yanagida, Hiroshi Taneichi, Katsumi HarimayaYuki Taniguchi, Hideki Shigematsu, Takahiro Iida, Satoru Demura, Ryo Sugawara, Nobuyuki Fujita, Mitsuru Yagi, Eijiro Okada, Naobumi Hosogane, Katsuki Kono, Masaya Nakamura, Kazuhiro Chiba, Toshiaki Kotani, Tsuyoshi Sakuma, Tsutomu Akazawa, Teppei Suzuki, Kotaro Nishida, Kenichiro Kakutani, Taichi Tsuji, Hideki Sudo, Akira Iwata, Tatsuya Sato, Satoshi Inami, Morio Matsumoto, Chikashi Terao, Kota Watanabe, Shiro Ikegawa

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Abstract

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

Original language	English
Article number	3685
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11596-w
Publication status	Published - 01-12-2019
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-019-11596-w

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Kou, I., Otomo, N., Takeda, K., Momozawa, Y., Lu, H. F., Kubo, M., Kamatani, Y., Ogura, Y., Takahashi, Y., Nakajima, M., Minami, S., Uno, K., Kawakami, N., Ito, M., Yonezawa, I., Watanabe, K., Kaito, T., Yanagida, H., Taneichi, H., ... Ikegawa, S. (2019). Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese. Nature communications, 10(1), Article 3685. https://doi.org/10.1038/s41467-019-11596-w

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title = "Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese",

abstract = "Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.",

author = "Ikuyo Kou and Nao Otomo and Kazuki Takeda and Yukihide Momozawa and Lu, {Hsing Fang} and Michiaki Kubo and Yoichiro Kamatani and Yoji Ogura and Yohei Takahashi and Masahiro Nakajima and Shohei Minami and Koki Uno and Noriaki Kawakami and Manabu Ito and Ikuho Yonezawa and Kei Watanabe and Takashi Kaito and Haruhisa Yanagida and Hiroshi Taneichi and Katsumi Harimaya and Yuki Taniguchi and Hideki Shigematsu and Takahiro Iida and Satoru Demura and Ryo Sugawara and Nobuyuki Fujita and Mitsuru Yagi and Eijiro Okada and Naobumi Hosogane and Katsuki Kono and Masaya Nakamura and Kazuhiro Chiba and Toshiaki Kotani and Tsuyoshi Sakuma and Tsutomu Akazawa and Teppei Suzuki and Kotaro Nishida and Kenichiro Kakutani and Taichi Tsuji and Hideki Sudo and Akira Iwata and Tatsuya Sato and Satoshi Inami and Morio Matsumoto and Chikashi Terao and Kota Watanabe and Shiro Ikegawa",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-11596-w",

language = "English",

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Kou, I, Otomo, N, Takeda, K, Momozawa, Y, Lu, HF, Kubo, M, Kamatani, Y, Ogura, Y, Takahashi, Y, Nakajima, M, Minami, S, Uno, K, Kawakami, N, Ito, M, Yonezawa, I, Watanabe, K, Kaito, T, Yanagida, H, Taneichi, H, Harimaya, K, Taniguchi, Y, Shigematsu, H, Iida, T, Demura, S, Sugawara, R, Fujita, N, Yagi, M, Okada, E, Hosogane, N, Kono, K, Nakamura, M, Chiba, K, Kotani, T, Sakuma, T, Akazawa, T, Suzuki, T, Nishida, K, Kakutani, K, Tsuji, T, Sudo, H, Iwata, A, Sato, T, Inami, S, Matsumoto, M, Terao, C, Watanabe, K & Ikegawa, S 2019, 'Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese', Nature communications, vol. 10, no. 1, 3685. https://doi.org/10.1038/s41467-019-11596-w

TY - JOUR

T1 - Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

AU - Kou, Ikuyo

AU - Otomo, Nao

AU - Takeda, Kazuki

AU - Momozawa, Yukihide

AU - Lu, Hsing Fang

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

AU - Ogura, Yoji

AU - Takahashi, Yohei

AU - Nakajima, Masahiro

AU - Minami, Shohei

AU - Uno, Koki

AU - Kawakami, Noriaki

AU - Ito, Manabu

AU - Yonezawa, Ikuho

AU - Watanabe, Kei

AU - Kaito, Takashi

AU - Yanagida, Haruhisa

AU - Taneichi, Hiroshi

AU - Harimaya, Katsumi

AU - Taniguchi, Yuki

AU - Shigematsu, Hideki

AU - Iida, Takahiro

AU - Demura, Satoru

AU - Sugawara, Ryo

AU - Fujita, Nobuyuki

AU - Yagi, Mitsuru

AU - Okada, Eijiro

AU - Hosogane, Naobumi

AU - Kono, Katsuki

AU - Nakamura, Masaya

AU - Chiba, Kazuhiro

AU - Kotani, Toshiaki

AU - Sakuma, Tsuyoshi

AU - Akazawa, Tsutomu

AU - Suzuki, Teppei

AU - Nishida, Kotaro

AU - Kakutani, Kenichiro

AU - Tsuji, Taichi

AU - Sudo, Hideki

AU - Iwata, Akira

AU - Sato, Tatsuya

AU - Inami, Satoshi

AU - Matsumoto, Morio

AU - Terao, Chikashi

AU - Watanabe, Kota

AU - Ikegawa, Shiro

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

AB - Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis-expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

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UR - http://www.scopus.com/inward/citedby.url?scp=85070777642&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-11596-w

DO - 10.1038/s41467-019-11596-w

M3 - Article

C2 - 31417091

AN - SCOPUS:85070777642

SN - 2041-1723

VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3685

ER -

Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese

Abstract

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