研究DNA甲基化年龄加速与阿尔茨海默病风险因素之间的关系。
Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer's disease.
作者信息
McCartney Daniel L, Stevenson Anna J, Walker Rosie M, Gibson Jude, Morris Stewart W, Campbell Archie, Murray Alison D, Whalley Heather C, Porteous David J, McIntosh Andrew M, Evans Kathryn L, Deary Ian J, Marioni Riccardo E
机构信息
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland.
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, Scotland.
出版信息
Alzheimers Dement (Amst). 2018 Jun 21;10:429-437. doi: 10.1016/j.dadm.2018.05.006. eCollection 2018.
INTRODUCTION
The "epigenetic clock" is a DNA methylation-based estimate of biological age and is correlated with chronological age-the greatest risk factor for Alzheimer's disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. In this study, we assess the relationship between the epigenetic clock and AD risk factors.
METHODS
Multilevel models were used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n = 5100).
RESULTS
We report significant associations between age acceleration and body mass index, total cholesterol to high-density lipoprotein cholesterol ratios, socioeconomic status, high blood pressure, and smoking behavior (Bonferroni-adjusted < .05).
DISCUSSION
Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.
引言
“表观遗传时钟”是基于DNA甲基化对生物年龄的一种估计，并且与实足年龄相关——实足年龄是阿尔茨海默病（AD）最大的风险因素。AD存在遗传和环境风险因素，其中一些是潜在可改变的。在本研究中，我们评估了表观遗传时钟与AD风险因素之间的关系。
方法
在“苏格兰一代”研究（n = 5100）中，使用多水平模型评估年龄加速（生物年龄回归到实足年龄的残差）与AD风险因素之间的关系，这些风险因素涉及认知储备、生活方式、疾病和遗传学。
结果
我们报告了年龄加速与体重指数、总胆固醇与高密度脂蛋白胆固醇比值、社会经济地位、高血压和吸烟行为之间存在显著关联（经Bonferroni校正，< 0.05）。
讨论
AD的环境风险因素与年龄加速之间存在关联。改变此类风险因素的措施可能会改善AD的风险状况以及生物衰老速率。因此，未来有必要进行纵向分析。
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