多组学联合分析研究世居藏族与移居者高原适应不全心肌损伤的表观遗传学机制

平均海拔4000米以上被称为“世界屋脊”青藏高原居住着以藏族为主的世居民族，是研究人群低氧适应的最佳群体。经过世代选择，世居藏族和移居高原的汉族较好的适应高原低氧环境，但是仍有一定比例出现对高原环境适应不全的现象。随着西部大开发战略和青藏铁路的开通，越来越多的平原人进入高原地区参与当地的经济建设甚至定居，对高原适应不全机制的研究越来越紧迫。高原低氧可直接影响心脏结构、血流动力学及心脏整体功能，造成心肌损伤，严重影响生活质量，甚至危及患者的生命。多项研究表明，长期低氧暴露对人体基因组DNA甲基化有重大影响，但既往研究多针对个别基因DNA甲基化水平的横断面研究，尚未有基因组层面的系统表观遗传学研究。本研究拟利用全基因组外显子测序、全基因组甲基化芯片和转录组测序技术，从多组学层面研究高原适应不全的表观遗传机制，对于高原病的预防诊断和治疗具有极高的科学意义和社会价值。

The Tibetan Plateau with an average altitude of over 4,000 meters，is known as the "Roof of the World", is inhabited by Tibetan, which is the best cohort to study the adaptation to hypoxia. The Tibetan and Han Chinese who migrated to the plateau have adapted better to the low oxygen environment after the selection of time, but a certain percentage of them are still not fully adapted to the plateau environment. With the Western Development Strategy and the opening of the Qinghai-Tibet Railway, more and more plainsmen are entering the plateau region to participate in work and even settlement, and the study of of plateau adaptation mechanism is becoming more and more urgent. The proto-hypoxic environment can directly affect cardiac structure, hemodynamics and overall cardiac function, causing myocardial damage, seriously affecting quality of life and even endangering the patients’ life. Several studies have shown that hypoxic exposure has a significant effect on human genomic DNA methylation levels and that epigenetic inheritance plays a very important role in plateau disease. However, cross-sectional studies on DNA methylation levels have been used in the past, and no genome-wide level phylogenetic epigenetic studies have been conducted. This study, with high scientific and social significance, proposes to investigate the epigenetic mechanisms of plateau adaptation deficits at a multi-omics level using whole-exome sequencing, whole-genome methylation microarray and transcriptome sequencing techniques.