title: Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3.
abstract: 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.
authors.affiliation: Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Science, Tokyo, Japan ; Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyake
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Yohei
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Todd A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.forename: Xusheng
authors.initials: X
authors.lastname: Qiu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Huang
authors.initials: H
authors.lastname: Yan
authors.forename: Katsuki
authors.initials: K
authors.lastname: Kono
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawakami
authors.forename: Koki
authors.initials: K
authors.lastname: Uno
authors.forename: Manabu
authors.initials: M
authors.lastname: Ito
authors.forename: Shohei
authors.initials: S
authors.lastname: Minami
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Yanagida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Taneichi
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Taichi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Teppei
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Sudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kotani
authors.forename: Ikuho
authors.initials: I
authors.lastname: Yonezawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Kota
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012600:Scoliosis / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
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