Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity

Kazuki Takeda, Ikuyo Kou, Naobumi Hosogane, Nao Otomo, Mitsuru Yagi, Shinjiro Kaneko, Hitoshi Kono, Masayuki Ishikawa, Yohei Takahashi, Takeshi Ikegami, Kenya Nojiri, Eijiro Okada, Haruki Funao, Kunimasa Okuyama, Takashi Tsuji, Nobuyuki Fujita, Narihito Nagoshi, Osahiko Tsuji, Yoji Ogura, Ken IshiiMasaya Nakamura, Morio Matsumoto, Shiro Ikegawa, Kota Watanabe

Research output: Contribution to journalArticle

Abstract

STUDY DESIGN: Genetic case-control study of single nucleotide polymorphisms (SNPs). OBJECTIVE: To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: ASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined. METHODS: ASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay. RESULTS: Among the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10, 1.00 × 10, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10) and with a left convex lumbar curve (P = 6.70 × 10), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10). CONCLUSION: rs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.4.

Original languageEnglish
Pages (from-to)1623-1629
Number of pages7
JournalSpine
Volume44
Issue number23
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Intervertebral Disc Degeneration
Scoliosis
Single Nucleotide Polymorphism
Genes
Case-Control Studies
Sample Size
Healthy Volunteers
Spine
Thorax

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Clinical Neurology

Cite this

Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity. / Takeda, Kazuki; Kou, Ikuyo; Hosogane, Naobumi; Otomo, Nao; Yagi, Mitsuru; Kaneko, Shinjiro; Kono, Hitoshi; Ishikawa, Masayuki; Takahashi, Yohei; Ikegami, Takeshi; Nojiri, Kenya; Okada, Eijiro; Funao, Haruki; Okuyama, Kunimasa; Tsuji, Takashi; Fujita, Nobuyuki; Nagoshi, Narihito; Tsuji, Osahiko; Ogura, Yoji; Ishii, Ken; Nakamura, Masaya; Matsumoto, Morio; Ikegawa, Shiro; Watanabe, Kota.

In: Spine, Vol. 44, No. 23, 01.12.2019, p. 1623-1629.

Research output: Contribution to journalArticle

Takeda, K, Kou, I, Hosogane, N, Otomo, N, Yagi, M, Kaneko, S, Kono, H, Ishikawa, M, Takahashi, Y, Ikegami, T, Nojiri, K, Okada, E, Funao, H, Okuyama, K, Tsuji, T, Fujita, N, Nagoshi, N, Tsuji, O, Ogura, Y, Ishii, K, Nakamura, M, Matsumoto, M, Ikegawa, S & Watanabe, K 2019, 'Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity', Spine, vol. 44, no. 23, pp. 1623-1629. https://doi.org/10.1097/BRS.0000000000003179
Takeda, Kazuki ; Kou, Ikuyo ; Hosogane, Naobumi ; Otomo, Nao ; Yagi, Mitsuru ; Kaneko, Shinjiro ; Kono, Hitoshi ; Ishikawa, Masayuki ; Takahashi, Yohei ; Ikegami, Takeshi ; Nojiri, Kenya ; Okada, Eijiro ; Funao, Haruki ; Okuyama, Kunimasa ; Tsuji, Takashi ; Fujita, Nobuyuki ; Nagoshi, Narihito ; Tsuji, Osahiko ; Ogura, Yoji ; Ishii, Ken ; Nakamura, Masaya ; Matsumoto, Morio ; Ikegawa, Shiro ; Watanabe, Kota. / Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity. In: Spine. 2019 ; Vol. 44, No. 23. pp. 1623-1629.
@article{844f6dfbff1e487b9aff852b0a8de829,
title = "Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity",
abstract = "STUDY DESIGN: Genetic case-control study of single nucleotide polymorphisms (SNPs). OBJECTIVE: To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: ASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined. METHODS: ASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay. RESULTS: Among the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10, 1.00 × 10, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10) and with a left convex lumbar curve (P = 6.70 × 10), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10). CONCLUSION: rs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.4.",
author = "Kazuki Takeda and Ikuyo Kou and Naobumi Hosogane and Nao Otomo and Mitsuru Yagi and Shinjiro Kaneko and Hitoshi Kono and Masayuki Ishikawa and Yohei Takahashi and Takeshi Ikegami and Kenya Nojiri and Eijiro Okada and Haruki Funao and Kunimasa Okuyama and Takashi Tsuji and Nobuyuki Fujita and Narihito Nagoshi and Osahiko Tsuji and Yoji Ogura and Ken Ishii and Masaya Nakamura and Morio Matsumoto and Shiro Ikegawa and Kota Watanabe",
year = "2019",
month = "12",
day = "1",
doi = "10.1097/BRS.0000000000003179",
language = "English",
volume = "44",
pages = "1623--1629",
journal = "Spine",
issn = "0362-2436",
publisher = "Lippincott Williams and Wilkins",
number = "23",

}

TY - JOUR

T1 - Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity

AU - Takeda, Kazuki

AU - Kou, Ikuyo

AU - Hosogane, Naobumi

AU - Otomo, Nao

AU - Yagi, Mitsuru

AU - Kaneko, Shinjiro

AU - Kono, Hitoshi

AU - Ishikawa, Masayuki

AU - Takahashi, Yohei

AU - Ikegami, Takeshi

AU - Nojiri, Kenya

AU - Okada, Eijiro

AU - Funao, Haruki

AU - Okuyama, Kunimasa

AU - Tsuji, Takashi

AU - Fujita, Nobuyuki

AU - Nagoshi, Narihito

AU - Tsuji, Osahiko

AU - Ogura, Yoji

AU - Ishii, Ken

AU - Nakamura, Masaya

AU - Matsumoto, Morio

AU - Ikegawa, Shiro

AU - Watanabe, Kota

PY - 2019/12/1

Y1 - 2019/12/1

N2 - STUDY DESIGN: Genetic case-control study of single nucleotide polymorphisms (SNPs). OBJECTIVE: To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: ASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined. METHODS: ASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay. RESULTS: Among the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10, 1.00 × 10, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10) and with a left convex lumbar curve (P = 6.70 × 10), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10). CONCLUSION: rs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.4.

AB - STUDY DESIGN: Genetic case-control study of single nucleotide polymorphisms (SNPs). OBJECTIVE: To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: ASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined. METHODS: ASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay. RESULTS: Among the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10, 1.00 × 10, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10) and with a left convex lumbar curve (P = 6.70 × 10), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10). CONCLUSION: rs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.4.

UR - http://www.scopus.com/inward/record.url?scp=85075105969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075105969&partnerID=8YFLogxK

U2 - 10.1097/BRS.0000000000003179

DO - 10.1097/BRS.0000000000003179

M3 - Article

C2 - 31365516

AN - SCOPUS:85075105969

VL - 44

SP - 1623

EP - 1629

JO - Spine

JF - Spine

SN - 0362-2436

IS - 23

ER -