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A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine

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Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common musculoskeletal disease among people after middle age. The OPLL presents with serious neurological abnormalities due to compression of the spinal cord and nerve roots. The OPLL is caused by genetic and environment factors; however, its etiology and pathogenesis still remain to be elucidated. To determine the susceptibility loci for OPLL, we performed a genome-wide linkage study using 214 affected sib-pairs of Japanese. In stratification analyses for definite cervical OPLL, we found loci with suggestive linkage on 1p21, 2p22–2p24, 7q22, 16q24 and 20p12. Fine mapping using additional markers detected the highest non-parametric linkage score (3.43, P = 0.00027) at D20S894 on chromosome 20p12 in a subgroup that had no complication of diabetes mellitus. Our result would shed a new light on genetic aspects of OPLL.

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Acknowledgments

We thank OPLL patients and their families who participated in this study and the Japan OPLL Network, including Ishikawa-prefecture OPLL Tomo-no-kai. We also thank members of the Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments. The work reported in this article was supported by a Grant for Intractable Diseases from the Public Health Bureau, the Ministry of Health and Welfare of Japan (Investigation Committee on Ossification of the Spinal Ligaments).

Conflict of interest

All authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Tatsuki Karasugi, Masahiro Nakajima & Shiro Ikegawa

  2. Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Tatsuki Karasugi & Hiroshi Mizuta

  3. Department of Orthopedic Surgery, Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan

    Katsunori Ikari

  4. Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan

    Takashi Tsuji, Morio Matsumoto, Kazuhiro Chiba & Yoshiaki Toyama

  5. Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Kenzo Uchida & Hisatoshi Baba

  6. Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan

    Yoshiharu Kawaguchi

  7. Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    Naoshi Ogata

  8. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Motoki Iwasaki

  9. Department of Medical Joint Materials, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan

    Shingo Maeda

  10. Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Takuya Numasawa

  11. Department of Spinal Reconstruction, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Kuniyoshi Abumi

  12. Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan

    Tsuyoshi Kato

  13. Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan

    Hiroshi Ozawa

  14. Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Toshihiko Taguchi

  15. Department of Orhopaedic Surgery, Osaka Minami Medical Center, Osaka, Japan

    Takashi Kaito

  16. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Masashi Neo

  17. Spine Section, Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

    Masashi Yamazaki

  18. Department of Orthopaedic Surgery, Kochi Medical School, Kochi, Japan

    Nobuaki Tadokoro

  19. Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan

    Munehito Yoshida

  20. National Hospital Organization Okayama Medical Center, Okayama, Japan

    Shinnosuke Nakahara

  21. Department Orthopaedic Surgery, Tokyo Medical University, Tokyo, Japan

    Kenji Endo

  22. Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shiro Imagama

  23. Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan

    Satoru Demura

  24. Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Japan

    Kimiaki Sato

  25. Department of Orthopaedics, Jichi Medical University, Shimono, Japan

    Atsushi Seichi

  26. Department of Orthopaedic Surgery, Kyorin University, Tokyo, Japan

    Shoichi Ichimura

  27. Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Isehara, Japan

    Masahiko Watanabe

  28. Department of Orthopaedic Surgery, Niigata University Medical and Dental General Hospital, Niigata, Japan

    Kei Watanabe

  29. Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan

    Yutaka Nakamura

  30. Department of Orthopaedic Surgery, Shiga University of Medical Science, Ohtsu, Japan

    Kanji Mori

Authors
  1. Tatsuki Karasugi
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  2. Masahiro Nakajima
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  3. Katsunori Ikari
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  4. Takashi Tsuji
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  5. Morio Matsumoto
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  6. Kazuhiro Chiba
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  7. Kenzo Uchida
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  8. Yoshiharu Kawaguchi
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  9. Hiroshi Mizuta
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  10. Naoshi Ogata
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  11. Motoki Iwasaki
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  12. Shingo Maeda
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  13. Takuya Numasawa
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  14. Kuniyoshi Abumi
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  15. Tsuyoshi Kato
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  16. Hiroshi Ozawa
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  17. Toshihiko Taguchi
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  18. Takashi Kaito
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  19. Masashi Neo
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  20. Masashi Yamazaki
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  22. Munehito Yoshida
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  28. Atsushi Seichi
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  30. Masahiko Watanabe
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  31. Kei Watanabe
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  32. Yutaka Nakamura
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  33. Kanji Mori
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  34. Hisatoshi Baba
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  35. Yoshiaki Toyama
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  36. Shiro Ikegawa
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Consortia

Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments

Corresponding author

Correspondence to Shiro Ikegawa.

Additional information

T. Karasugi and M. Nakajima contributed equally to this work.

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Karasugi, T., Nakajima, M., Ikari, K. et al. A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Metab 31, 136–143 (2013). https://doi.org/10.1007/s00774-012-0404-y

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  • DOI: https://doi.org/10.1007/s00774-012-0404-y

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