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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

ABSTRACT: Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P?=?2.95?×?10-20; odds ratio?=?1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.

SUBMITTER: Kou I

PROVIDER: S-EPMC6070519 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

Kou Ikuyo I Watanabe Kota K Takahashi Yohei Y Momozawa Yukihide Y Khanshour Anas A Grauers Anna A Zhou Hang H Liu Gang G Fan Yan-Hui YH Takeda Kazuki K Ogura Yoji Y Zhou Taifeng T Iwasaki Yusuke Y Kubo Michiaki M Wu Zhihong Z Matsumoto Morio M Einarsdottir Elisabet E Kere Juha J Huang Dongsheng D Qiu Guixing G Qiu Yong Y Wise Carol A CA Song You-Qiang YQ Wu Nan N Su Peiqiang P Gerdhem Paul P Ikegawa Shiro S

Scientific reports 20180801 1

Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Norther ...[more]

PMID: 30069010

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Project description:The Ladybird Homeobox 1 (LBX1) gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). The association between LBX1 gene polymorphisms and AIS has been investigated in several studies. However, these findings have yield contradictory results rather than conclusive evidence.This study is to provide a meta-analysis of the published case-control studies on the association between LBX1 gene polymorphisms and AIS in Asian and Caucasian populations.This meta-analysis conformed to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a literature research on PubMed, Embase, Web of Science, and Cochrane Library until February 10, 2018. We included all case-control or cohort studies about association between LBX1 gene polymorphisms and AIS. The Risk Of Bias In Non-randomised Studies-of Interventions and Critical Appraisal Skills Programme were used to evaluate the risk of bias and study quality. We assessed the strength of association by pooled odds ratios (ORs) and 95% confidence intervals (CIs) in all genetic models under a fixed-effect model or random-effect model. We further performed subgroup analysis by ethnicity and sex. Sensitivity analysis and publication bias were also undertaken.A total of 10 studies (11,411 cases and 26,609 controls) were included in this meta-analysis. The pooled results showed a statistically significant association between LBX1 gene polymorphisms and AIS (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001). For stratified analyses by ethnicity and sex, robust significant associations were detected in Asian and Caucasian populations, and in women and men under all genetic models.T allele of rs11190870 and G alleles of rs625039 and rs11598564 represent risk factors for AIS, but G allele of rs678741 may play a protective role in the occurrence of AIS. Further research is needed to confirm this finding and to understand its implications.

Project description:AimTo evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.MethodsSelection criteria(1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other.Search methodOvid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.ResultsThe review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.ConclusionThis review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.

Project description:BackgroundAdolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in children and adolescents which presents as complex three-dimensional (3D) deformity of the spine and rib cage. This study aimed to estimate the effectiveness and safety of surgical interventions for AIS using Bayesian meta-analysis.MethodsThe PubMed, EMBASE, and Cochrane Controlled Register of Trials were searched through Oct 1, 2019, without language restrictions. Relevant studies evaluating combined effectiveness and safety of surgical interventions for AIS were included according to eligibility criteria. The primary outcome measures included pulmonary function (change of absolute forced vital capacity and forced expiratory volume in 1 second from pre-operation to post-operation) and incidence of complications. The secondary outcome measure was change of Cobb angle from pre-operation to post-operation. Data was pooled using a random effects model in pairwise meta-analysis. Bayesian meta-analysis combined direct and indirect evidence using a Bayesian framework.ResultsTwenty-eight case-controlled studies with totally 1970 participants were included. This Bayesian meta-analysis combining direct and indirect evidences indicated that posterior fusion with instrumentation without thoracoplasty (PSF) had the highest probability to achieve better pulmonary function and lower complication rate; video assisted anterior fusion with instrumentation without thoracoplasty (VAT) had the highest probability to obtain better Cobb angle correction based on analysis of rank probability.ConclusionThis Bayesian meta-analysis demonstrated that PSF had the highest probability to achieve better post-surgical pulmonary function and lower complication rate, which gives a practical recommendation of PSF as a primary surgical treatment for AIS. The results also support statistics that current surgeries adopted more PSF but less open anterior approach surgery and thoracoplasty. More research work is required to address the effectiveness and safety of VAT for treating AIS more convincingly.

Dataset Information

A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

Publications

A multi-ethnic meta-analysis confirms the association of rs6570507 with adolescent idiopathic scoliosis.

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