Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults
Association between epigenetic age acceleration and depressive symptoms in a prospective cohort study of urban-dwelling adults
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DOI：
10.1016/j.jad.2019.06.032
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发表时间：
2019-10-01
影响因子：
6.6
通讯作者：
Zonderman, Alan B.
中科院分区：
文献类型：
--
作者：
Beydoun, May A.;Hossain, Sharmin;Zonderman, Alan B.
目的：本研究测试协会的DNA甲基化为基础的（DNAm）措施的表观遗传年龄加速（EAA）与横截面和纵向抑郁症状在城市样本的中年adultes.Methods：白色和非洲裔美国成年人参与者在健康老龄化的多样性社区的整个寿命研究，其中DNA样本进行了分析（基线年龄：30-65岁），我们包括。我们估计了三种基于DNAm的EAA指标：（1）普遍表观遗传年龄加速（EAA Accel）;（2）内在表观遗传年龄加速（IEAA）;和（3）外在表观遗传年龄加速（EEAA）。在基线（2004-2009）和随访访视（2009-2013）时，使用20项流行病学中心抑郁量表总分和子域评分评估抑郁症状。进行线性混合效应回归模型，调整潜在的混杂协变量，选择偏倚和多重检验（N = 329名参与者，类似于52%的男性，k = 1.9观察/参与者，平均随访时间类似于4.7年）。IEAA --一种衡量细胞表观遗传年龄加速的指标，与白色血细胞成分无关--在总人群中与“积极影响”的减少有横断面相关性（γ（011）+/- SE = -0.090 +/- 0.030，P = 0.003，Cohen's D：-0.16），白人中（gamma（011）+/- SE = -0.135 +/- 0.048，P = 0.005，Cohen's D：-0.23）。基线“积极影响”与ESTA Accel.Limitations类似：局限性包括小样本量，弱-中度影响和测量误差。结论：使用Horvath算法的两种EAA测量方法IEAA和EAA Accel与总体和白人中减少的“积极影响”有关。未来的研究需要复制我们的发现并测试双向关系。
Objective: This study tests associations of DNA methylation-based (DNAm) measures of epigenetic age acceleration (EAA) with cross-sectional and longitudinal depressive symptoms in an urban sample of middle-aged adults.Methods: White and African-American adult participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study for whom DNA samples were analyzed (baseline age: 30-65 years) we included. We estimated three DNAm based EAA measures: (1) universal epigenetic age acceleration (AgeAccel); (2) intrinsic epigenetic age acceleration (IEAA); and (3) extrinsic epigenetic age acceleration (EEAA). Depressive symptoms were assessed using the 20-item Center for Epidemiological Studies-Depression scale total and sub-domain scores at baseline (2004-2009) and follow-up visits (2009-2013). Linear mixed-effects regression models were conducted, adjusting potentially confounding covariates, selection bias and multiple testing (N = 329 participants, similar to 52% men, k = 1.9 observations/participant, mean follow-up time similar to 4.7 years).Results: None of the epigenetic age acceleration measures were associated with total depressive symptom scores at baseline or over time. IEAA - a measure of cellular epigenetic age acceleration irrespective of white blood cell composition - was cross-sectionally associated with decrement in "positive affect" in the total population (gamma(011) +/- SE = -0.090 +/- 0.030, P = 0.003, Cohen's D: -0.16) and among Whites (gamma(011)+/- SE = -0.135 +/- 0.048, P = 0.005, Cohen's D: - 0.23), after correction for multiple testing. Baseline "positive affect" was similarly associated with AgeAccel.Limitations: Limitations included small sample size, weak-moderate effects and measurement error. Conclusions: IEAA and AgeAccel, two measures of EAA using Horvath algorithm, were linked to a reduced "positive affect", overall and among Whites. Future studies are needed to replicate our findings and test bidirectional relationships.