先天性心脏病是最严重的出生缺陷之一。高原地区由于低氧环境所造成的先心病发病特点与平原地区有明显差异，提示了其中可能存在的特异性分子遗传机制。针对藏族等高原世居民族的高原适应性的全基因组水平分析已经揭示了一系列适应高原低氧环境相关的基因。在这其中，EPAS1基因可能在心脏早期发育过程起着重要作用。本课题组前期研究结果初步提示了EPAS1基因可能与藏族先心病发病相关。在此基础上，本研究计划针对青海藏族大样本先心病病例采用三步法，即"关联分析初步筛选-相关变异位点上下游序列重测序-细胞水平功能验证"，系统深入的研究EPAS1基因与高原环境下先心病发病的潜在分子遗传关联，为高原环境下先心病的早期诊治等提供理论依据。

Congenital heart disease (CHD) is one of the most serious birth defects. CHD caused by low oxygen levels in high altitude areas shows different traits from that found in plain inhabitants, indicating that a specific molecular genetic mechanism might exist. The analysis of adaptability-related whole genome of ethnic groups, such as the Tibetans, who have lived on plateaus for generations, has identified a series of adaptability-related genes, among which EPAS1 is likely to have played a key role in the early-stage development of human heart. Our previous research suggests that EPAS1 might be related to the development of CHD among the Tibetan ethnics, building on which this study intends to analyze the vast samples of CHD among Qinghai Tibetans in three steps, namely "preliminary screening based on relevancy analysis, resequencing genes upstream and downstream variable sites , and cell level verification", so as to identify the underlying molecular genetic relevance between EPAS1 and plateau dweller CHD, and thus provide theoretical basis for early diagnosis and treatment of the disease.