Journal Article

A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine

Karasugi, Tatsuki, Takahata, Masahiko, Nakajima, Masahiro, Kashii, Masafumi, Seichi, Atsushi, Chiba, Kazuhiro, Tsuji, Takashi, Matsumoto, Morio, Baba, Hisatoshi, Kida, Kazunobu, Uchida, Kenzo, Kaito, Takashi, Kawaguchi, Yoshiharu, Kobayashi, Sho, Taniguchi, Yuki, Takahashi, Atsushi, Kubo, Michiaki, Takahashi, Masahito, Mori, Kanji, Furukawa, Ken-Ichi, Toyama, Yoshiaki, Okawa, Atsushi, Yamada, Kei, Takeuchi, Kazuhiro, Nakajima, Hideaki, Fujibayashi, Shunsuke, Watanabe, Kei, Kawabata, Shigenori, Ito, Zenya, Ikegawa, Shiro, Kanchiku, Tsukasa, Tanaka, Toshihiro, Maeda, Shingo, Shindo, Shigeo

2014

Overview

Shiro Ikegawa and colleagues report the results of a genome-wide association study for ossification of the posterior longitudinal ligament of the spine in a Japanese cohort. They identify six new loci, three of which showed decreased expression in a mouse model of endochondral ossification. 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/39 / 38/43 / 38/88 / 692/699/1670/122 / Agriculture / Analysis / Animal Genetics and Genomics / Biomedicine / Cancer Research / Case-Control Studies / Cell division / Disease susceptibility / Elderly / Etiology / Etiology (Medicine) / Female / Gene expression / Gene Function / Genes / Genetic aspects / Genetic factors / Genetic Loci / Genetic Predisposition to Disease / Genetic research / Genome-wide association studies / Genome-Wide Association Study - methods / Genomes / Genomics / Human Genetics / Humans / Identification and classification / letter / Male / Methods / Middle Aged / Ossification of Posterior Longitudinal Ligament - genetics / Ossification of Posterior Longitudinal Ligament - pathology / Pathogenesis / Polymorphism, Single Nucleotide / Proteins / Quantitative trait loci / Risk factors / Software / Spinal diseases / Spine / Spine - pathology / Studies