title: A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine.
abstract: Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common spinal disorder among the elderly that causes myelopathy and radiculopathy. To identify genetic factors for OPLL, we performed a genome-wide association study (GWAS) in ∼8,000 individuals followed by a replication study using an additional ∼7,000 individuals. We identified six susceptibility loci for OPLL: 20p12.3 (rs2423294: P = 1.10 × 10(-13)), 8q23.1 (rs374810: P = 1.88 × 10(-13)), 12p11.22 (rs1979679: P = 4.34 × 10(-12)), 12p12.2 (rs11045000: P = 2.95 × 10(-11)), 8q23.3 (rs13279799: P = 1.28 × 10(-10)) and 6p21.1 (rs927485: P = 9.40 × 10(-9)). Analyses of gene expression in and around the loci suggested that several genes are involved in OPLL etiology through membranous and/or endochondral ossification processes. Our results bring new insight to the etiology of OPLL.
authors: 1] Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan. [2].
authors: Masahiro
authors: M
authors: Nakajima
authors: 1] Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan. [2].
authors: Atsushi
authors: A
authors: Takahashi
authors: 1] Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan. [2].
authors: Takashi
authors: T
authors: Tsuji
authors: 1] Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan. [2] Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Tatsuki
authors: T
authors: Karasugi
authors: Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors: Hisatoshi
authors: H
authors: Baba
authors: Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors: Kenzo
authors: K
authors: Uchida
authors: Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Shigenori
authors: S
authors: Kawabata
authors: Department of Orthopaedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Okawa
authors: Department of Orthopedics, Kudanzaka Hospital, Tokyo, Japan.
authors: Shigeo
authors: S
authors: Shindo
authors: Department of Orthopaedic Surgery, National Okayama Medical Center, Okayama, Japan.
authors: Kazuhiro
authors: K
authors: Takeuchi
authors: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Taniguchi
authors: Department of Medical Joint Materials, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Shingo
authors: S
authors: Maeda
authors: Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Masafumi
authors: M
authors: Kashii
authors: Department of Orthopedics, Jichi Medical University, Shimotsuke, Japan.
authors: Atsushi
authors: A
authors: Seichi
authors: Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors: Hideaki
authors: H
authors: Nakajima
authors: Department of Orthopaedic Surgery, Toyama University, Toyama, Japan.
authors: Yoshiharu
authors: Y
authors: Kawaguchi
authors: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Shunsuke
authors: S
authors: Fujibayashi
authors: Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Masahiko
authors: M
authors: Takahata
authors: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Toshihiro
authors: T
authors: Tanaka
authors: Department of Orthopaedic Surgery, Niigata University Medical and Dental General Hospital, Niigata, Japan.
authors: Kei
authors: K
authors: Watanabe
authors: Department of Orthopaedic Surgery, Kochi Medical School, Kochi, Japan.
authors: Kazunobu
authors: K
authors: Kida
authors: Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Tsukasa
authors: T
authors: Kanchiku
authors: Department of Orthopedics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Zenya
authors: Z
authors: Ito
authors: Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Japan.
authors: Kanji
authors: K
authors: Mori
authors: Department of Orthopaedic Surgery, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan.
authors: Takashi
authors: T
authors: Kaito
authors: Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Sho
authors: S
authors: Kobayashi
authors: Department of Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Japan.
authors: Kei
authors: K
authors: Yamada
authors: Department of Orthopaedic Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors: Masahito
authors: M
authors: Takahashi
authors: 1] Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan. [2].
authors: Kazuhiro
authors: K
authors: Chiba
authors: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors: Morio
authors: M
authors: Matsumoto
authors: Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Ken-Ichi
authors: K
authors: Furukawa
authors: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors: Michiaki
authors: M
authors: Kubo
authors: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors: Yoshiaki
authors: Y
authors: Toyama
authors: Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
authors: Shiro
authors: S
authors: Ikegawa
mesh_terms: D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013131:Spine / Q000473:pathology