青少年特发性脊柱侧凸（AIS）是脊柱外科的难题，对社会和家庭造成沉重负担，探索其早期诊断和治疗靶点是当前研究热点。其发生除与遗传因素相关外，表观遗传学也发挥重要作用，但具体机制尚不明确。同卵双胞胎由于其遗传背景完全相同，是表观遗传学理想的研究对象。前期工作中，我们已建立AIS队列，并发现5对AIS正常-患病同卵双胞胎，应用WGBS对其中1对进行测序分析，结果显示两者存在可能与AIS相关的全基因组DNA甲基化水平差异，并发现差异区域部分位于SNP附近。因此，本项目以“全基因组表观遗传学变异结合SNP可能导致AIS的发病”为假说，采用全基因组甲基化测序方法，通过对比表型分离的同卵双胞胎差异，结合SNP并进行大样本及细胞功能验证，寻找并阐明与AIS发生相关的表观遗传学及SNP因素，建立SNP-DNA methylation-AIS临床表型调控网络，为AIS的预防和早期诊治提供新的思路和靶点。

Adolescent idiopathic scoliosis is a complicated spinal discord for spine surgeons, and is a heavy burden on society and families. It has become the current research hotspot of AIS to explore its early diagnosis and treatment targets. The genesis of scoliosis is related to not only genetics but also epigenetics. However, the molecular mechanism underlining its pathogenesis is not well known. In our previous study, we have set up an AIS cohort and found 5 monozygotic twins, of which one was diagnosed with AIS, and the other was normal. We use WGBS to perform methylation analysis, the difference of whole-genome DNA methylation between the twins was significant, and some of the DMR located nearby SNP. Therefore, we presumed that epigenetics mutation and SNP might have a pivotal role in AIS. Based on our previous study, we hypothesize that epigenetics mutation combing with SNP could lead to the development of AIS. The techniques of WGBS and the strategy of MZ twins will be used to explore the epigenetic and SNP factors of AIS. SNP-DNA methylation-AIS clinical phenotype Regulation network will be built. Up to now, there was no study on the whole genome epigenetic research about AIS. This study will give a new insight into the etiology of AIS and provide a new way for the early diagnosis, treatment, and prevention of AIS.