Replication Study for the Association of GWAS-associated Loci With Adolescent Idiopathic Scoliosis Susceptibility and Curve Progression in a Chinese Population

被引:21
作者
Man, Gene Chi-Wai [1 ,2 ,6 ]
Tan, Nelson Leung-Sang [3 ,6 ,7 ]
Chan, Ting Fung [4 ]
Lam, Tsz Ping [1 ,6 ]
Li, Jing Woei [4 ]
Ng, Bobby Kin-Wah [1 ,6 ]
Zhu, Zezhang [5 ,6 ]
Qiu, Yong [5 ,6 ]
Cheng, Jack Chun-Yiu [1 ,6 ]
机构
[1] Chinese Univ Hong Kong, Prince Wales Hosp, SH Ho Scoliosis Res Lab, Dept Orthopaed & Traumatol,Fac Med,Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Fac Med, Prince Wales Hosp,Shatin, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Dept Chem Pathol,Shatin, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Fac Sci, Sch Life Sci, Hong Kong, Peoples R China
[5] Nanjing Univ, Med Sch, Dept Spine Surg, Affiliated Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China
[6] Joint Scoliosis Res Ctr Chinese Univ Hong Kong Na, Hong Kong, Peoples R China
[7] Chinese Univ Hong Kong, Fac Med, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
adolescent idiopathic scoliosis; Chinese; curve progression; curve severity; genome-wide association study; replication study; single nucleotide polymorphisms; skeletal maturity; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; PROMOTER POLYMORPHISM; GENETIC POLYMORPHISMS; PROGNOSTIC TEST; GPR126; GENE; LBX1; LOCUS; RS11190870; METAANALYSIS; VARIANTS;
D O I
10.1097/BRS.0000000000002866
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Study Design. A genetic association (replication) study. Objective. The aim of this study was to replicate and further evaluate the association among seven genome-wide association studies (GWAS)-identified single nucleotide polymorphisms (SNPs) in Chinese girls with adolescent idiopathic scoliosis (AIS) with disease onset, curve types, and progression. Summary of Background Data. AIS is the most common pediatric spinal deformity with a strong genetic predisposition. Recent GWAS identified 10 new disease predisposition loci for AIS. Methods. Three hundred nineteen female AIS patients with Cobb angle 10 o and 201 healthy controls were studied for the association with disease onset. Seven GWAS-identified SNPs (rs11190870 in LBX1, rs12946942 in SOX9/ KCNJ2, rs13398147 in PAX3/ EPH4, rs241215 in AJAP1, rs3904778 in BNC2, rs6570507 in GPR126, and rs678741 in LBX1-AS1) were analyzed. In subgroup analysis, AIS patients were subdivided by curve types and disease progression to examine for genotype association. Results. We replicated the association with disease onset in four common SNPs rs11190870, rs3904778, rs6570507, and rs678741. In addition, rs1190870 and rs678741 remained significantly associated in the right thoracic curves only subgroup. However, no significant difference was observed with both clinical curve progression or Cobb angle. Conclusion. This study replicated the associations of four GWAS-associated SNPs with occurrence of AIS in our Chinese population. However, none of these SNPs was associated with curve severity and progression. The results suggest that curve progression may be determined by environmental (nongenetic) factor, but further study with a larger sample size is required to address this issue.
引用
收藏
页码:464 / 471
页数:8
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