成年双生子血压水平与DNA甲基化相关性研究  

Correlation between blood pressure and DNA methylation in adult twins

作　　者：吴震天 高文静[1] 王碧琦[1] 曹卫华[1] 吕筠[1] 余灿清[1] 逄增昌[2] 丛黎明[3] 汪华[4] 吴先萍[5] 李立明[1] WU Zhen-tian1, GAO Wen-jing1, WANG Bi-qi1, CAO Wei-hua1, LV Jun1, YU Can-qing1, PANG Zeng-chang2, CONG Li-ming3, WANG Hua4,WU Xian -ping5,LI Li-ming1(1. Department of Epidemiologyand Biostatistics,Peking University School of Public Healtli,Beijing 100191,ChiQingdao Municipal Center for Disease Control and Prevention,Qingdao 266033, Shandong, China; 3. Zhejiang Center forDisease Control and Prevention,Hangzhou 310051, China; 4. Jiangsu Center for Disease Control and 210009,China; 5. Sichuan Center for Disease Control and Prevention,Chengdu 610041,Chin)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]青岛市疾病预防控制中心,山东青岛266033 [3]浙江省疾病预防控制中心,杭州310051 [4]江苏省疾病预防控制中心,南京210009 [5]四川省疾病预防控制中心,成都610041

出　　处：《北京大学学报（医学版）》2018年第3期387-394,共8页Journal of Peking University:Health Sciences

基　　金：公益性行业科研专项(201502006;201002007);国家自然科学基金(81573223)资助~~

摘　　要：目的:在成年双生子人群中探索与血压指标(收缩压、舒张压、平均动脉压、脉压)存在相关性的DNA甲基化位点。方法:研究人群来自中国双生子登记系统,共476名双生子,问卷调查包括一般人口学特征、生活方式及疾病状况等信息,体格检查包括血压、身高、体重等信息,使用Infinium Human Methylation450 Bead Chip芯片对外周全血进行全基因组DNA甲基化检测。在调整潜在混杂因素的基础上,通过构建混合效应模型在全基因组范围寻找与血压指标存在相关性的DNA甲基化位点,显著性水平为错误发现阳性位点率<0.05。结果:经过数据质量控制最终纳入465名双生子(122对同卵双生子,104对异卵双生子,13对双生子的其中之一),年龄(44.8±13.2)岁,男性多于女性,同卵略多于异卵,目前吸烟和目前规律饮酒者所占比例均大于30%。所有双生子个体均行全基因组DNA甲基化与血压指标相关分析,经多重校正后未发现显著的甲基化位点,但位于10号染色体的cg07761116在3个血压指标(收缩压、舒张压、平均动脉压)相关分析中的P值相对较小,提示其可能是一个与血压相关的位点。还有7个位点在两个血压指标相关分析中的P值较小,所在基因与神经发育、蛋白质稳态、炎症反应等功能相关。结论:没有明确证据支持与血压水平存在相关性的甲基化位点,可能由于样本量不足等原因,可以为后续开展类似的双生子研究提供参考,后续研究可以关注10号染色体上的cg07761116及其他P值较小的位点。Objective： To explore the DNA methylation sites correlated with blood pressure（ systolic blood pressure,diastolic blood pressure,mean arterial pressure,pulse pressure） in adult twin population. Methods： A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics,lifestyle,disease status and other information,and blood pressure,height,weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium Human Methylation450 Bead Chip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors,and the significant level was false discovery rate 0. 05. Results： After data quality control,465 twins（ 122 pairs of monozygotic twins,104 pairs of dizygotic twins,13 individuals from 13 pairs of twins） aged（ 44. 8 ±13. 2） years were finally enrolled. There were more males and more monozygotic twins,and the current smokers and current regular drinkers both accounted for more than 30%. No significant Cp G site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However,the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices（ systolic blood pressure,diastolic blood pressure,mean arterial pressure）,suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices,respectively,which pointed to genes involved in neurological development,protein homeostasis,inflammatory reaction and other pathways. Conclusion： There is no sufficient evidence to support any DNA methylation site correlated with blood pressure,which may be caused by insufficient sample size and other reasons. This study could provide a

关 键 词：血压 DNA甲基化 双生子研究 

分 类 号：R181.3[医药卫生—流行病学]