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加速的 DNA 甲基化年龄:与创伤后应激障碍和死亡率的关联。

Accelerated DNA Methylation Age: Associations With Posttraumatic Stress Disorder and Mortality.

机构信息

From the National Center for PTSD (Wolf, Logue, Sadeh, Hayes, Miller), Behavioral Science Division, VA Boston Healthcare System; Department of Psychiatry (Wolf, Sadeh, Hayes, Miller), Boston University School of Medicine; Biomedical Genetics (Logue), Boston University School of Medicine; Department of Biostatistics (Logue), Boston University School of Public Health; Research Service (Stoop), VA Boston Healthcare System; and Pharmacogenomics Analysis Laboratory (Schichman, Stone), Research Service, Central Arkansas Veterans Healthcare System, Boston, Massachusetts.

出版信息

Psychosom Med. 2018 Jan;80(1):42-48. doi: 10.1097/PSY.0000000000000506.

Abstract

OBJECTIVE

Recently developed indices of cellular age based on DNA methylation (DNAm) data, referred to as DNAm age, are being used to study factors that influence the rate of aging and the health correlates of these metrics of the epigenetic clock. This study evaluated associations between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and accelerated versus decelerated DNAm age among military veterans. We also examined whether accelerated DNAm age predicted mortality over the course of a 6.5-year medical record review period.

METHODS

Three hundred thirty-nine genotype-confirmed white, non-Hispanic, middle-aged, trauma-exposed veterans underwent psychiatric assessment and genome-wide DNAm analysis. DNAm age was calculated using a previously validated algorithm. Medical records were available for a subset of 241 veterans and were reviewed approximately 6.5 years after DNA collection and PTSD assessment.

RESULTS

PTSD hyperarousal symptoms were associated with accelerated DNAm age (β = 0.20, p = .009) but trauma exposure and total PTSD severity were not. Accelerated DNAm age was also associated with 13% increased risk for all-cause mortality (hazard ratio = 1.13, 95% confidence interval = 1.01-1.26) during the medical record review period.

CONCLUSIONS

Findings of this study replicate the association between PTSD and accelerated DNAm age and suggest that this effect may be specific to the hyperarousal symptom cluster. Results point to the potential utility of DNAm age algorithms for identifying individuals who are aging at an accelerated rate and for determining the factors that influence this process.

摘要

目的

最近基于 DNA 甲基化(DNAm)数据开发的细胞年龄指数,称为 DNAm 年龄,正被用于研究影响衰老速度的因素,以及这些表观遗传时钟指标与健康的相关性。本研究评估了创伤暴露、创伤后应激障碍(PTSD)症状与军事退伍军人中加速或减速 DNAm 年龄之间的关系。我们还研究了加速的 DNAm 年龄是否可以预测在 6.5 年的医疗记录审查期间的死亡率。

方法

339 名经基因确认的白种、非西班牙裔、中年、创伤暴露的退伍军人接受了精神病学评估和全基因组 DNAm 分析。使用先前验证的算法计算 DNAm 年龄。部分 241 名退伍军人有医疗记录,在 DNA 采集和 PTSD 评估后大约 6.5 年进行了审查。

结果

PTSD 警觉过度症状与加速的 DNAm 年龄相关(β=0.20,p=0.009),但创伤暴露和 PTSD 总严重程度则没有。加速的 DNAm 年龄与全因死亡率增加 13%也相关(危险比=1.13,95%置信区间=1.01-1.26)在医疗记录审查期间。

结论

本研究的结果复制了 PTSD 与加速的 DNAm 年龄之间的关联,并表明这种影响可能特定于警觉过度症状群。研究结果表明,DNAm 年龄算法可能对识别加速衰老的个体以及确定影响这一过程的因素具有潜在的效用。

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