中国汉族人群非综合征型唇腭裂的全基因组关联研究

非综合征型唇腭裂是一种遗传和环境共同作用的多因素复杂疾病。最近全基因组关联研究发现多个与唇腭裂易感性有关的单核苷酸多态性位点，但是这些研究大多数在欧美人群中进行，本课题组对这些易感位点分别进行了验证，但是结果并不一致，而中国人群与欧美人群具有不同的遗传背景，因此有必要寻找与中国汉族人群特有的遗传易感性基因。本项目拟采用大样本的两阶段的病例－对照研究和核心家系，通过全基因组关联策略研究与唇腭裂易感性有关的SNPs，分析评价基因型－临床表型以及基因－基因和基因－环境的交互作用，在此基础上，通过一系列分子生物学实验进一步探讨SNPs的生物学功能。本研究将有助于阐明唇腭裂的遗传因素及其可能的分子机制，对唇腭裂患者早期筛检和个体化预防与治疗具有重要的意义。

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a complex disease with documented genetic and environmental risk factors. Recently, genome-wide association study (GWAS) has found several single nucleotide polymorphisms (SNPs) associated with NSCL/P risk. However, these studies were mostly performed among Caucasians. Our previous studies have replicated GWAS findings on NSCL/P in our Chinese populations with the inconsistent results. Because of diverse ethnic background in a Chinese population, it is necessary to find the novel susceptibility genes for NSCL/P. This study will conduct a GWAS for NSCL/P in a two-stage case-control subjects and family trios with large sample size. Furthermore, we will explore the associations between the genotypes and clinical phenotypes, gene-gene, and gene-environment interactions. We also determine the functionality of these significant SNPs by using a series of molecular biological assays. Our results will elucidate the genetic factors and mechanisms of NSCL/P, and contribute to the early screening and individual therapy.