Area of Cardiometabolic and Renal Risk, Biomedical Research Institute Hospital Clinic of Valencia (INCLIVA), Av. Menendez Pelayo 4 accesorio, 46010, Valencia, Spain.
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA.
Curr Environ Health Rep. 2019 Mar;6(1):38-51. doi: 10.1007/s40572-019-0226-3.
Epigenetic modifications are environmentally responsive and may play a mechanistic role in the development of disease. Mendelian randomization uses genetic variation to assess the causal effect of modifiable exposures on health outcomes. We conducted a systematic review of Mendelian randomization studies evaluating the causal role of DNA methylation (DNAm) changes on the development of health states, emphasizing on studies that formally evaluate exposure-DNAm, in addition to DNAm-outcome, causal associations.
We identified 15 articles, 4 of them including an environmental determinant of DNAm, including self-reported tobacco smoke exposure, in utero tobacco smoke exposure, measured vitamin B, and glycemia. Selected articles suggest a causal association of DNAm with some cardiometabolic endpoints. DNAm seemed to partly explain the association of postnatal and prenatal exposure to tobacco smoke and vitamin B with inflammation biomarkers, birth weight, and cognitive outcomes, respectively. However, the current evidence is not sufficient to infer causality. Additional Mendelian randomization studies from large epidemiologic samples are needed to support the causal role of environmental factors as determinants of health-related epigenetic modifications.
表观遗传修饰是对环境有反应的，可能在疾病的发展中起机械作用。孟德尔随机化利用遗传变异来评估可改变的暴露对健康结果的因果影响。我们进行了一项系统综述，评估了 DNA 甲基化 (DNAm) 变化对健康状态发展的因果作用的孟德尔随机化研究，强调了除 DNAm-结局外，还正式评估暴露-DNAm 因果关系的研究。
我们确定了 15 篇文章，其中 4 篇包括 DNAm 的环境决定因素，包括自我报告的吸烟暴露、宫内吸烟暴露、测量的维生素 B 和血糖。一些选定的文章表明 DNAm 与一些心血管代谢终点之间存在因果关系。DNAm 似乎部分解释了出生后和产前暴露于烟草烟雾和维生素 B 与炎症生物标志物、出生体重和认知结果之间的关联。然而，目前的证据还不足以推断因果关系。需要来自大型流行病学样本的额外孟德尔随机化研究来支持环境因素作为与健康相关的表观遗传修饰决定因素的因果作用。
