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成年双胞胎中血压与DNA甲基化之间的相关性

[Correlation between blood pressure and DNA methylation in adult twins].

作者信息

Wu Z T, Gao W J, Wang B Q, Cao W H, Lv J, Yu C Q, Pang Z C, Cong L M, Wang H, Wu X P, Li L M

机构信息

Department of Epidemiologyand Biostatistics, Peking University School of Public Health, Beijing 100191, China.

Qingdao Municipal Center for Disease Control and Prevention, Qingdao 266033, Shandong, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2018 Jun 18;50(3):387-394.

Abstract

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 HumanMethylation450 BeadChip. 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 CpG 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 reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.

摘要

目的

探讨成年双胞胎人群中与血压(收缩压、舒张压、平均动脉压、脉压)相关的DNA甲基化位点。

方法

从中国国家双胞胎登记处选取476对双胞胎作为研究对象。采用问卷调查收集人口统计学特征、生活方式、疾病状况等信息,并测量血压、身高、体重等人体测量指标。使用Infinium HumanMethylation450 BeadChip检测全血样本的全基因组DNA甲基化。通过构建混合效应模型并调整潜在混杂因素,分析与血压相关的DNA甲基化位点,显著水平为错误发现率<0.05。

结果

经过数据质量控制,最终纳入465对双胞胎(122对同卵双胞胎,104对异卵双胞胎,来自13对双胞胎的13名个体),年龄为(44.8±13.2)岁。男性和同卵双胞胎较多,当前吸烟者和当前经常饮酒者均占30%以上。在使用所收集的双胞胎进行的全基因组DNA甲基化与血压相关性研究中,多次检验后未发现显著的CpG位点。然而,位于10号染色体上的cg07761116在3个血压指标(收缩压、舒张压、平均动脉压)的相关性分析中P值较低,提示该位点可能与血压相关。另外7个位点分别在两个血压指标的相关性分析中P值较低,指向涉及神经发育、蛋白质稳态、炎症反应等途径的基因。

结论

尚无充分证据支持任何与血压相关的DNA甲基化位点,这可能是由于样本量不足等原因所致。本研究可为后续类似的双胞胎研究提供参考,后续研究可关注位于10号染色体上的cg07761116及其他P值较低的位点。

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