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

Research output: Contribution to journalArticle

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 languageEnglish
Article number3685
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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genome
Genome-Wide Association Study
Scoliosis
loci
Genes
magnetic permeability
Pediatrics
Uric Acid
etiology
pathogenesis
Meta-Analysis
uric acid
cells
genes
Quantitative Trait Loci
proportion
Body Mass Index
acids

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese. / Kou, Ikuyo; Otomo, Nao; Takeda, Kazuki; Momozawa, Yukihide; Lu, Hsing Fang; Kubo, Michiaki; Kamatani, Yoichiro; Ogura, Yoji; Takahashi, Yohei; Nakajima, Masahiro; Minami, Shohei; Uno, Koki; Kawakami, Noriaki; Ito, Manabu; Yonezawa, Ikuho; Watanabe, Kei; Kaito, Takashi; Yanagida, Haruhisa; Taneichi, Hiroshi; Harimaya, Katsumi; Taniguchi, Yuki; Shigematsu, Hideki; Iida, Takahiro; Demura, Satoru; Sugawara, Ryo; Fujita, Nobuyuki; Yagi, Mitsuru; Okada, Eijiro; Hosogane, Naobumi; Kono, Katsuki; Nakamura, Masaya; Chiba, Kazuhiro; Kotani, Toshiaki; Sakuma, Tsuyoshi; Akazawa, Tsutomu; Suzuki, Teppei; Nishida, Kotaro; Kakutani, Kenichiro; Tsuji, Taichi; Sudo, Hideki; Iwata, Akira; Sato, Tatsuya; Inami, Satoshi; Matsumoto, Morio; Terao, Chikashi; Watanabe, Kota; Ikegawa, Shiro.

In: Nature communications, Vol. 10, No. 1, 3685, 01.12.2019.

Research output: Contribution to journalArticle

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
Kou, Ikuyo ; Otomo, Nao ; Takeda, Kazuki ; Momozawa, Yukihide ; Lu, Hsing Fang ; Kubo, Michiaki ; Kamatani, Yoichiro ; Ogura, Yoji ; Takahashi, Yohei ; Nakajima, Masahiro ; Minami, Shohei ; Uno, Koki ; Kawakami, Noriaki ; Ito, Manabu ; Yonezawa, Ikuho ; Watanabe, Kei ; Kaito, Takashi ; Yanagida, Haruhisa ; Taneichi, Hiroshi ; Harimaya, Katsumi ; Taniguchi, Yuki ; Shigematsu, Hideki ; Iida, Takahiro ; Demura, Satoru ; Sugawara, Ryo ; Fujita, Nobuyuki ; Yagi, Mitsuru ; Okada, Eijiro ; Hosogane, Naobumi ; Kono, Katsuki ; Nakamura, Masaya ; Chiba, Kazuhiro ; Kotani, Toshiaki ; Sakuma, Tsuyoshi ; Akazawa, Tsutomu ; Suzuki, Teppei ; Nishida, Kotaro ; Kakutani, Kenichiro ; Tsuji, Taichi ; Sudo, Hideki ; Iwata, Akira ; Sato, Tatsuya ; Inami, Satoshi ; Matsumoto, Morio ; Terao, Chikashi ; Watanabe, Kota ; Ikegawa, Shiro. / Genome-wide association study identifies 14 previously unreported susceptibility loci for adolescent idiopathic scoliosis in Japanese. In: Nature communications. 2019 ; Vol. 10, No. 1.
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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.",
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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.

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