Identification of a Susceptibility Locus for Severe Adolescent Idiopathic Scoliosis on Chromosome 17q24.3

نویسندگان

  • Atsushi Miyake
  • Ikuyo Kou
  • Yohei Takahashi
  • Todd A. Johnson
  • Yoji Ogura
  • Jin Dai
  • Xusheng Qiu
  • Atsushi Takahashi
  • Hua Jiang
  • Huang Yan
  • Katsuki Kono
  • Noriaki Kawakami
  • Koki Uno
  • Manabu Ito
  • Shohei Minami
  • Haruhisa Yanagida
  • Hiroshi Taneichi
  • Naoya Hosono
  • Taichi Tsuji
  • Teppei Suzuki
  • Hideki Sudo
  • Toshiaki Kotani
  • Ikuho Yonezawa
  • Michiaki Kubo
  • Tatsuhiko Tsunoda
  • Kota Watanabe
  • Kazuhiro Chiba
  • Yoshiaki Toyama
  • Yong Qiu
  • Morio Matsumoto
  • Shiro Ikegawa
چکیده

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013