北京市儿童青少年双生子肥胖与DNA甲基化相关性研究

The situation of obesity remains very serious around the world including China nowadays. Obesity is not only a chronic outcome, but also closely associated with diabetes, hypertension, cancer and other chronic diseases. Traditional research indicates that obesity is the result of the interaction of genetic and environmental factors. However, most research just focuses on the effect sizes of genetic elements or which environmental elements are affecting obesity, and there is no unified conclusion so far when mentioning the specific Epigenetic changes associated with genetic or environmental factors. Up to now, DNA methylation has been the most common Epigenetic factors studied. Since twins', especially monozygotic twins' genetic structure is the same, they are widely used in the field of Genetic Epidemiology. Compared with adults, child and adolescent twins can partially avoid the impact of the complex environmental factors to the level of DNA methylation. This study will select 100 child and adolescent twin pairs including MZ and DZ in Being, collect their questionnaires and physical examination, then explore the obesity-related methylation sites and their levels; the association among environmental factors and obesity-related methylation sites and their levels. This study will be the first Genomewide DNA methylation study which focuses on obesity in child and adolescent twins in China.

目前肥胖在世界范围内的形势仍然严峻，肥胖不仅是一种慢性结局，同时还与糖尿病、高血压、肿瘤等其它慢性病密切相关。传统研究表明，肥胖是遗传和环境共同作用的结果，而截至目前，多数研究仍局限于遗传影响大小以及哪些环境因素会对于肥胖产生影响，具体到遗传和环境影响后的表观遗传学改变则尚无统一结论。到目前为止，DNA甲基化是最常见、研究最多的表观遗传现象。而双生子，尤其是同卵双生子，可以控制基因结构相同，在遗传流行病学领域当中得到广泛的应用。同时，儿童青少年双生子与成年双生子又避免了复杂环境对于DNA甲基化水平的影响。本研究将在北京选取90对在校儿童青少年双生子，利用问卷调查和体检结果，在区分同卵、异卵双生子后，探索与肥胖（以BMI、腰围、腰臀比和体脂百分含量为指标）相关的甲基化位点和水平以及环境因素与肥胖相关甲基化位点和水平的关系。本研究将是国内首个以儿童青少年双生子为研究对象的DNA甲基化研究。

本研究在北京市朝阳区、延庆区及房山区招募90对6~17周岁双生子，首先对其基本情况分布特征及其甲基化分布特征进行描述，然后基于23对肥胖不一致的双生子，在全基因组范围内探索与儿童青少年肥胖相关的DNA甲基化位点及其甲基化水平。质量控制后共有179名合格双生子个体进入后续分析。肥胖作为连续变量，利用179名个体信息，构建混合效应模型分析单个甲基化位点与BMI、WC及PBF相关性；肥胖作为分类变量，利用23对肥胖不一致同卵双生子对进行配对t检验；肥胖作为分类变量，利用23对肥胖不一致同卵双生子进行肥胖组与非肥胖组间DNA甲基化变异水平差异分析。经过多重校正后，未发现满足显著性水平的甲基化位点。但关联分析显示位于2号染色体ADD2基因上的位点cg19076706可能与肥胖发生相关，提示后续研究可以继续关注，并可为后续此类利用肥胖不一致的儿童青少年双生子研究提供方法学参考。