Dataset Information

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

ABSTRACT: 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.

SUBMITTER: Ogura Y

PROVIDER: S-EPMC4573260 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Ogura Yoji Y Kou Ikuyo I Miura Shigenori S Takahashi Atsushi A Xu Leilei L Takeda Kazuki K Takahashi Yohei Y Kono Katsuki K Kawakami Noriaki N Uno Koki K Ito Manabu M Minami Shohei S Yonezawa Ikuho I Yanagida Haruhisa H Taneichi Hiroshi H Zhu Zezhang Z Tsuji Taichi T Suzuki Teppei T Sudo Hideki H Kotani Toshiaki T Watanabe Kota K Hosogane Naobumi N Okada Eijiro E Iida Aritoshi A Nakajima Masahiro M Sudo Akihiro A Chiba Kazuhiro K Hiraki Yuji Y Toyama Yoshiaki Y Qiu Yong Y Shukunami Chisa C Kamatani Yoichiro Y Kubo Michiaki M Matsumoto Morio M Ikegawa Shiro S

American journal of human genetics 20150723 2

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 susceptibi ...[more]

PMID: 26211971

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Project description:BackgroundDespite more than a century of dedicated research, the etiology and pathogenesis of adolescent idiopathic scoliosis (AIS) remain unclear. By definition, 'idiopathic' implies an unknown cause. Nevertheless, many abnormalities concomitant to AIS have been described, often with the suggestion that these abnormalities are related to etio-pathogenesis. Insight in the concomitant abnormalities may assist in improving the understanding of the etiological pathways of AIS. We aimed to systematically review and synthesize available studies on abnormalities concomitant to AIS.MethodsOriginal studies comparing untreated AIS patients with healthy adolescents on abnormalities other than the deformity of the spine were retrieved from PubMed and Embase. We followed PRISMA guidelines and to quantify the relationship between each abnormality and AIS we used a best-evidence-syntheses for relating risk-of-bias to consistency of effect sizes.ResultsWe identified 88 relevant citations, forty-seven carried high risk-of-bias and twenty studies did not report quantitative data in a sufficient manner. The remaining twenty-one publications failed to report data from before initiation of the deformity and blind assessments. These cross-sectional studies provided data on fourteen abnormalities concomitant to AIS. With our best-evidence-syntheses we were unable to find both strong evidence and a consistent pattern of occurrence for AIS and any of these abnormalities. From moderate risk-of-bias studies a relatively consistent pattern of occurrence for AIS and impaired gait control (4 studies; 155 subjects; Cohen's d = 1.00) and decreased bone mineral density (2 studies; 954 subjects; Cohen's d =?-0.83) was found. For nine abnormalities a consistent pattern of occurrence with AIS was found, but the evidence for these was weak.ConclusionsBased on the available literature, strong evidence is lacking for a consistent pattern of occurrence of AIS and any abnormality. The relevance for understanding the multifactorial etiology of AIS is very limited.

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A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Publications

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

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