Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls.

Zezhang Zhu,Zhen Zhang,Feng Zhu,Xiao Han,Zhonghui Chen,Xiaodong Qin,Jiang Chang,Zongshan Hu,Wen Zhang,Zhou Wang,Yueming Song,K M Lee,Fangcai Li,Yang Yu,Mengran Jin,Ling Chen,Saihu Mao,Bing Wang,Dingding Xie,Long Yi,Yong Qiu,Long Jiang,Zhen Liu,Peng Liu,Xu Sun,Fei Wang,Limin Liu,Xusheng Qiu,Benlong Shi,Leilei Xu,Wayne Lee ,Nelson L.s Tang ,Jie Qiao ,Tp Lam ,Bobby Kin Wah Ng ,Bang Ping Qian ,Jack C Y Cheng

doi:10.1038/ncomms9355

Abstract

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.

Highlights

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children
906,703 single nucleotide polymorphisms (SNPs) were genotyped in 1,001 patients presenting a main thoracic curve and 1,500 healthy controls
Some signs of regulatory activity, including histone modifications at promoter or enhancer, DNase hypersensitivity sites, binding proteins and motifs changed, were observed for the four associated SNPs and their surrogates (Supplementary Tables 5–8). In this four-stage genome-wide association study (GWAS), we identified four SNPs that are significantly associated with risk of AIS in the Chinese population

Summary

Introduction

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. We refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined 1⁄4 9.68 Â 10 À 37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS. Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine that is estimated to affect millions of children, with a prevalence of 2–4% (refs 1,2). Understood as a complex trait (polygenic disease), the genetic aetiology of AIS has been widely investigated by linkage analysis and candidate gene association analysis[3,4,5]

Methods

Results

Conclusion