Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.

Adolescent idiopathic scoliosis is a pediatric spinal deformity affecting 2-3% of school-age children worldwide(1). Genetic factors have been implicated in its etiology(2). Through a genome-wide association study (GWAS) and replication study involving a total of 1,376 Japanese females with adolescent idiopathic scoliosis and 11,297 female controls, we identified a locus at chromosome 10q24.31 associated with adolescent idiopathic scoliosis susceptibility. The most significant SNP (rs11190870; combined P = 1.24 × 10(-19); odds ratio (OR) = 1.56) is located near LBX1 (encoding ladybird homeobox 1). The identification of this susceptibility locus provides new insights into the pathogenesis of adolescent idiopathic scoliosis.

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.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Several AIS susceptibility loci have been identified; however, they could explain only a small proportion of AIS heritability. To identify additional AIS susceptibility loci, we conduct a meta-analysis of the three genome-wide association studies consisting of 79,211 Japanese individuals. We identify 20 loci significantly associated with AIS, including 14 previously not reported loci. These loci explain 4.6% of the phenotypic variance of AIS. We find 21 cis -expression quantitative trait loci-associated genes in seven of the fourteen loci. By a female meta-analysis, we identify additional three significant loci. We also find significant genetic correlations of AIS with body mass index and uric acid. The cell-type specificity analyses show the significant heritability enrichment for AIS in multiple cell-type groups, suggesting the heterogeneity of etiology and pathogenesis of AIS. Our findings provide insights into etiology and pathogenesis of AIS.

Since the residual apical translation of the main thoracic curve and the lowest instrumented vertebra more cranial to the last touching vertebra were significantly associated with adding-on, surgeons may need to obtain the maximum reduction of the apical translation of the main thoracic curve and to extend the LIV at least to the LTV to avoid postoperative adding-on.

Increases in the upper thoracic scoliotic curve, thoracic kyphosis, and number of rod-lengthening procedures are positively associated with an increased risk of complications after GR surgery for EOS.

Adolescent idiopathic scoliosis (AIS) is a common disorder with a strong genetic predisposition. Associations between AIS and common single nucleotide polymorphisms (SNPs) in estrogen receptor genes have been reported. rs9340799 in the gene for estrogen receptor a (ESR1) is reported to be associated with curve severity in Japanese and with AIS predisposition and curve severity in Chinese. In addition, rs1256120 in the gene for estrogen receptor b (ESR2) is reported to be associated with AIS predisposition and curve severity in Chinese. However, the sample sizes of these previous studies were small, and the associations of these SNPs have not been replicated. To examine the association between AIS and estrogen receptor genes, we investigated the association of rs9340799 and rs1256120 with AIS predisposition and curve severity using a large Japanese population, consisting of 798 AIS patients and 637 sex-matched controls. We found no association of either SNP with AIS predisposition or curve severity in the Japanese population. Considering the statistical power of the present study and the limitations of the previous reports, we conclude that the associations of rs9340799 and rs1256120 with AIS predisposition and curve severity are negative. ß

Purpose The surgical strategy for cervical spondylotic myelopathy (CSM) accompanying local kyphosis is controversial. The purpose of the present study was to compare and evaluate the outcomes of two types of surgery for CSM accompanying local kyphosis: (1) laminoplasty alone (LP) and (2) posterior reconstruction surgery (PR) in which we corrected the local kyphosis using a pedicle screw or lateral mass screw. Methods Sixty patients who presented with local kyphosis exceeding 5°were enrolled. LP and PR were each performed on a group of 30 of these patients; 30 CSM patients without local kyphosis, who had undergone LP, were used as controls. The follow-up period was 2 years or longer. Preoperative local kyphosis angles in LP and PR were 8.3°± 4.4°and 8.8°± 5.7°, respectively. Preoperative C2-7 angles in LP, PR and controls were -1.7°± 9.6°, -0.4°± 7.2°and -12.0°± 5.6°, respectively. The recovery rate of the JOA score, local kyphosis angle and C2-7 angle at post-op and follow-up were compared between the groups. Results The recovery rate of the JOA score in the LP group (32.6 %) was significantly worse than that in the PR group (44.5 %) and that of controls (53.8 %). Local kyphosis angles in the PR and LP groups at follow-up were 4.0°± 8.6°and 8.0°± 6.0°, respectively. However, although the C2-7 angle at follow-up was improved to -11.1°± 12.7°in PR, and maintained at -11.6°± 6.2°in controls, it deteriorated to 0.5°± 12.7°in LP. Conclusions The present study is the first to compare the outcomes between LP alone and PR for CSM accompanying local kyphosis. It revealed that PR resulted in a better clinical outcome than did LP alone. This result may be due to reduction of local kyphosis, stabilization of the unstable segment, and/or the maintenance of C2-7 angle until follow-up in the PR group.