GWAS-associated Single Nucleotide Polymorphisms are associated with Curve Progression in Adolescent Idiopathic Scoliosis?
Refereed conference paper presented and published in conference proceedings


Although there have been many genes associated with patients with adolescent idiopathic scoliosis (AIS) from different genomewide association studies (GWAS), there has been no replication study for validating their association with curve severity and curve progression.
The 8 GWAS-associated single nucleotide polymorphisms (SNPs) are associated with curve severity and curve progression in female Chinese AIS.
Genetic association study of 8 GWAS-associated SNPs previously reported to be associated with adolescent idiopathic scoliosis in the Chinese population.
This study aimed to determine whether there is association of the 8 SNPS generated from our GWAS study in Chinese AIS with curve progression.
We recruited 201 non-AIS female controls and 319 female AIS patients with a Cobb angle of 10o or greater. The AIS patients were further subdivided into progressive and non-progressive groups: 1) scoliotic curves 40o or greater were regarded as progressive group, and 2) scoliotic curves less than 40o and had reached skeletal maturation were classified as non-progressive group. We then evaluated the association of 8 SNPs (rs11190870 in LBX1, rs12946942 in SOX9/KCJN2, rs13398147 in PAX3/ EPHA4, rs241215 in AJAP1, rs3904778 in BNC2, rs6137473 in PAX1, rs6570507 in GPR126, and rs678741 in LBX1-AS1) by comparing risk allele frequencies between the 1) AIS and non-AIS groups and 2) compared between progressive Vs non-progressive groups, and with the mean Cobb angle for each genotype.
We evaluated the non-AIS controls and AIS subjects, the risk allele frequencies were significantly different for 4 SNPs namely LBX1 (p<0.01), BNC2 (p<0.05), GPR126 (p<0.05), and LBX1-AS1 (p<0.01). When comparing between the progressive AIS (N = 114) with non-progressive AIS (N = 205) subjects, the risk allele frequency for LBX1-AS1 was shown to be marginally associated. The mean Cobb angle for each genotype did not showed statistical difference.
This is the first study to validate and report the associations of the 4 GWAS-associated SNPs between AIS and non-AIS controls in the Chinese population. In addition, the SNP encoding for LBX1-AS1 was marginally associated with curve progression in AIS. Further replication study across different ethnic groups would be necessary to clarify whether these SNPs could potentially be genetic markers for predicting the occurrence/progression of AIS and institute appropriate timely treatment.
著者Gene Chi Wai Man, Nelson Leung Sang Tang, Ting Fung Chan, Bobby Kin-wah Ng, Lei-Lei Xu, Tsz-Ping Lam, ZeZhang Zhu, Yong Qiu, Jack C.Y. Cheng, Wayne YW Lee
會議名稱52nd Scoliosis Research Society Annual Meeting & Course
會議論文集題名Proceedings of the 52nd Scoliosis Research Society Annual Meeting & Course
頁次247 - 248

上次更新時間 2018-07-06 於 16:34