A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine

Taizo Horikoshi, Koichi Maeda, Yoshiharu Kawaguchi, Kazuhiro Chiba, Kanji Mori, Yu Koshizuka, Shigeru Hirabayashi, Kazuhito Sugimori, Morio Matsumoto, Hiroshi Kawaguchi, Makoto Takahashi, Hisashi Inoue, Tomoatsu Kimura, Yoshitaka Matsusue, Itsuro Inoue, Hisatoshi Baba, Kozo Nakamura, Shiro Ikegawa

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the χ2 test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P = 0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

Original languageEnglish
Pages (from-to)611-616
Number of pages6
JournalHuman Genetics
Volume119
Issue number6
DOIs
Publication statusPublished - 2006 Jul

Fingerprint

Genetic Association Studies
Longitudinal Ligaments
Spine
Single Nucleotide Polymorphism
Genes
Transforming Growth Factor beta3
Ossification of the posterior longitudinal ligament of the spine
Case-Control Studies
Research

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Horikoshi, T., Maeda, K., Kawaguchi, Y., Chiba, K., Mori, K., Koshizuka, Y., ... Ikegawa, S. (2006). A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Human Genetics, 119(6), 611-616. https://doi.org/10.1007/s00439-006-0170-9

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. / Horikoshi, Taizo; Maeda, Koichi; Kawaguchi, Yoshiharu; Chiba, Kazuhiro; Mori, Kanji; Koshizuka, Yu; Hirabayashi, Shigeru; Sugimori, Kazuhito; Matsumoto, Morio; Kawaguchi, Hiroshi; Takahashi, Makoto; Inoue, Hisashi; Kimura, Tomoatsu; Matsusue, Yoshitaka; Inoue, Itsuro; Baba, Hisatoshi; Nakamura, Kozo; Ikegawa, Shiro.

In: Human Genetics, Vol. 119, No. 6, 07.2006, p. 611-616.

Research output: Contribution to journalArticle

Horikoshi, T, Maeda, K, Kawaguchi, Y, Chiba, K, Mori, K, Koshizuka, Y, Hirabayashi, S, Sugimori, K, Matsumoto, M, Kawaguchi, H, Takahashi, M, Inoue, H, Kimura, T, Matsusue, Y, Inoue, I, Baba, H, Nakamura, K & Ikegawa, S 2006, 'A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine', Human Genetics, vol. 119, no. 6, pp. 611-616. https://doi.org/10.1007/s00439-006-0170-9
Horikoshi, Taizo ; Maeda, Koichi ; Kawaguchi, Yoshiharu ; Chiba, Kazuhiro ; Mori, Kanji ; Koshizuka, Yu ; Hirabayashi, Shigeru ; Sugimori, Kazuhito ; Matsumoto, Morio ; Kawaguchi, Hiroshi ; Takahashi, Makoto ; Inoue, Hisashi ; Kimura, Tomoatsu ; Matsusue, Yoshitaka ; Inoue, Itsuro ; Baba, Hisatoshi ; Nakamura, Kozo ; Ikegawa, Shiro. / A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. In: Human Genetics. 2006 ; Vol. 119, No. 6. pp. 611-616.
@article{5feb8440a2e54e128b07e79cb759a039,
title = "A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine",
abstract = "Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the χ2 test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P = 0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.",
author = "Taizo Horikoshi and Koichi Maeda and Yoshiharu Kawaguchi and Kazuhiro Chiba and Kanji Mori and Yu Koshizuka and Shigeru Hirabayashi and Kazuhito Sugimori and Morio Matsumoto and Hiroshi Kawaguchi and Makoto Takahashi and Hisashi Inoue and Tomoatsu Kimura and Yoshitaka Matsusue and Itsuro Inoue and Hisatoshi Baba and Kozo Nakamura and Shiro Ikegawa",
year = "2006",
month = "7",
doi = "10.1007/s00439-006-0170-9",
language = "English",
volume = "119",
pages = "611--616",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine

AU - Horikoshi, Taizo

AU - Maeda, Koichi

AU - Kawaguchi, Yoshiharu

AU - Chiba, Kazuhiro

AU - Mori, Kanji

AU - Koshizuka, Yu

AU - Hirabayashi, Shigeru

AU - Sugimori, Kazuhito

AU - Matsumoto, Morio

AU - Kawaguchi, Hiroshi

AU - Takahashi, Makoto

AU - Inoue, Hisashi

AU - Kimura, Tomoatsu

AU - Matsusue, Yoshitaka

AU - Inoue, Itsuro

AU - Baba, Hisatoshi

AU - Nakamura, Kozo

AU - Ikegawa, Shiro

PY - 2006/7

Y1 - 2006/7

N2 - Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the χ2 test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P = 0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

AB - Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the χ2 test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P = 0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

UR - http://www.scopus.com/inward/record.url?scp=33744462657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744462657&partnerID=8YFLogxK

U2 - 10.1007/s00439-006-0170-9

DO - 10.1007/s00439-006-0170-9

M3 - Article

VL - 119

SP - 611

EP - 616

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 6

ER -