Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Int J Epidemiol. 2019 Dec 1;48(6):1958-1971. doi: 10.1093/ije/dyz082.
A 'mortality risk score' (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality.
Among 534 males aged 55-85 years from the US Normative Aging Study, the MS, DNAmAge and DNAmPhenoAge were derived from blood DNA methylation profiles from the Illumina HumanMethylation450 BeadChip, and TL was measured by quantitative real-time polymerase chain reaction (qRT-PCR).
A total of 147 participants died during a median follow-up of 9.4 years. The MS showed strong associations with all-cause, cardiovascular disease (CVD) and cancer mortality. After controlling for all potential covariates, participants with high MS (>5 CpG sites with aberrant methylation) had almost 4-fold all-cause mortality (hazard ratio: 3.84, 95% confidence interval: 1.92-7.67) compared with participants with a low MS (0-1 CpG site with aberrant methylation). Similar patterns were observed with respect to CVD and cancer mortality. MS was associated with TL and DNAmPhenoAge acceleration but not with DNAmAge acceleration. Although the MS and DNAmPhenoAge acceleration were independently associated with all-cause mortality, the former exhibited a higher predictive accuracy of mortality than the latter.
MS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings.
先前基于十个与死亡率相关的胞嘧啶-磷酸-鸟嘌呤（CpG）位点的“死亡率风险评分（MS）”与全因死亡率相关，但尚未经外部验证。我们旨在验证 MS 与死亡率的相关性，并将 MS 与三种衰老生物标志物（端粒长度（TL）、DNA 甲基化年龄（DNAmAge）和表型年龄（DNAmPhenoAge）进行比较，以探讨 MS 是否可作为生物衰老和死亡率的可靠衡量标准。
在美国常规衰老研究中，从 Illumina HumanMethylation450 BeadChip 血液 DNA 甲基化谱中得出 534 名年龄在 55-85 岁的男性的 MS、DNAmAge 和 DNAmPhenoAge，并用定量实时聚合酶链反应（qRT-PCR）测量 TL。
在中位随访 9.4 年期间，共有 147 名参与者死亡。MS 与全因、心血管疾病（CVD）和癌症死亡率密切相关。在控制所有潜在协变量后，MS 较高（>5 个 CpG 位点异常甲基化）的参与者全因死亡率几乎增加了 4 倍（风险比：3.84，95%置信区间：1.92-7.67），而 MS 较低（0-1 个 CpG 位点异常甲基化）的参与者。在 CVD 和癌症死亡率方面也观察到了类似的模式。MS 与 TL 和 DNAmPhenoAge 加速相关，但与 DNAmAge 加速无关。尽管 MS 和 DNAmPhenoAge 加速与全因死亡率独立相关，但前者对死亡率的预测准确性高于后者。
MS 有可能成为死亡率的重要预测指标，可增强临床环境中的生存预测。
