A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis

Yoji Ogura, Ikuyo Kou, Shigenori Miura, Atsushi Takahashi, Leilei Xu, Kazuki Takeda, Yohei Takahashi, Katsuki Kono, Noriaki Kawakami, Koki Uno, Manabu Ito, Shohei Minami, Ikuho Yonezawa, Haruhisa Yanagida, Hiroshi Taneichi, Zezhang Zhu, Taichi Tsuji, Teppei Suzuki, Hideki Sudo, Toshiaki KotaniKota Watanabe, Naobumi Hosogane, Eijiro Okada, Aritoshi Iida, Masahiro Nakajima, Akihiro Sudo, Kazuhiro Chiba, Yuji Hiraki, Yoshiaki Toyama, Yong Qiu, Chisa Shukunami, Yoichiro Kamatani, Michiaki Kubo, Morio Matsumoto, Shiro Ikegawa

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10-13; odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.

Original languageEnglish
Article number1911
Pages (from-to)337-342
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished - 2015 Aug 6

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis'. Together they form a unique fingerprint.

Cite this