文章摘要
李春晓,高莹,高文静,余灿清,吕筠,吕若然,段佳丽,孙颖,郭向晖,王胜锋,周斌,王观,曹卫华,李立明.7~16岁儿童青少年肥胖与DNA甲基化相关性的双生子研究[J].中华流行病学杂志,2018,39(4):443-448
7~16岁儿童青少年肥胖与DNA甲基化相关性的双生子研究
Association between obesity and DNA methylation among the 7-16 year-old twins
收稿日期:2017-09-12  出版日期:2018-04-18
DOI:10.3760/cma.j.issn.0254-6450.2018.04.011
中文关键词: 肥胖  全基因组DNA甲基化  表观遗传学  儿童青少年  双生子
英文关键词: Obesity  Genome-wide DNA Methylation  Children and adolescents  Epigenetics  Twins
基金项目:国家自然科学基金(81473041);公益性行业科研专项(201502006,201002007)
作者单位E-mail
李春晓 100191 北京大学公共卫生学院流行病与卫生统计学系  
高莹 100191 北京大学公共卫生学院流行病与卫生统计学系  
高文静 100191 北京大学公共卫生学院流行病与卫生统计学系  
余灿清 100191 北京大学公共卫生学院流行病与卫生统计学系  
吕筠 100191 北京大学公共卫生学院流行病与卫生统计学系  
吕若然 100013 北京市疾病预防控制中心  
段佳丽 100013 北京市疾病预防控制中心  
孙颖 100013 北京市疾病预防控制中心  
郭向晖 100021 北京市朝阳区疾病预防控制中心  
王胜锋 100191 北京大学公共卫生学院流行病与卫生统计学系  
周斌 100191 北京大学公共卫生学院流行病与卫生统计学系  
王观 100013 北京市疾病预防控制中心  
曹卫华 100191 北京大学公共卫生学院流行病与卫生统计学系 caoweihua60@163.com 
李立明 100191 北京大学公共卫生学院流行病与卫生统计学系  
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中文摘要:
      目的 基于肥胖不一致双生子人群,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。方法 2016年在北京市朝阳区、延庆区及房山区招募90对6~17周岁双生子,通过问卷调查和体格检查收集双生子个人信息以及身高、体重、腰围等;通过美国Illumina公司EPIC芯片进行全基因组甲基化检测,采用R 3.3.1软件进行DNA甲基化数据读取、质量控制和统计学分析。利用肥胖不一致同卵双生子对,采用经验贝叶斯配对调整t检验和Levene检验,分别探索与肥胖相关的DNA甲基化差异位点和DNA甲基化变异差异位点。结果 根据研究定义,共纳入23对肥胖不一致同卵双生子对,年龄范围7~16岁。共有817 471个合格CpG位点纳入全基因组相关分析,未发现满足多重校正标准的肥胖相关DNA甲基化阳性位点,P值最小的DNA甲基化差异位点为12号染色体上的位点cg05684382(P=1.26E-06,FDR>0.05),P值最小的DNA甲基化变异差异位点为16号染色体CMIP基因主体上的位点cg26188191(P=6.44E-06,FDR>0.05),均为EPIC芯片新增位点。结论 基于本研究人群,研究未发现满足显著性要求的肥胖相关DNA甲基化阳性位点,但分析提示cg05684382、cg26188191可能与肥胖发生相关。
英文摘要:
      Objective On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr:12) and cg26188191 (chr:16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
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