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: Masahiro Nakajima, Atsushi Takahashi, Takashi Tsuji, Tatsuki Karasugi, Hisatoshi Baba, Kenzo Uchida, Shigenori Kawabata, Atsushi Okawa, Shigeo Shindo, Kazuhiro Takeuchi, Yuki Taniguchi, Shingo Maeda, Masafumi Kashii, Atsushi Seichi, Hideaki Nakajima, Yoshiharu Kawaguchi, Shunsuke Fujibayashi, Masahiko Takahata, Toshihiro Tanaka, Kei Watanabe, Kazunobu Kida, Tsukasa Kanchiku, Zenya Ito, Kanji Mori, Takashi Kaito, Sho Kobayashi, Kei Yamada, Masahito Takahashi, Kazuhiro Chiba, Morio Matsumoto, Ken-Ichi Furukawa, Michiaki Kubo, Yoshiaki Toyama, Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments, Shiro Ikegawa
• Journal: Nature genetics (Nat Genet) Vol. 46 Issue 9 Pg. 1012-6 (Sep 2014) ISSN: 1546-1718 [Electronic] United States
• PMID: 25064007 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Topics

• Case-Control Studies
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study (methods)
• Humans
• Male
• Middle Aged
• Ossification of Posterior Longitudinal Ligament (genetics, pathology)
• Polymorphism, Single Nucleotide
• Spine (pathology)