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Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males

Citation:

Gao X, Colicino E, Shen J, Just AC, Nwanaji-Enwerem JC, Wang C, Coull B, Lin X, Vokonas P, Zheng Y, et al. Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males. Int J Epidemiol [Internet]. 2019;48:1958-1971.

摘要:

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: MS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings.

附注:

Gao, Xu Colicino, Elena Shen, Jincheng Just, Allan C Nwanaji-Enwerem, Jamaji C Wang, Cuicui Coull, Brent Lin, Xihong Vokonas, Pantel Zheng, Yinan Hou, Lifang Schwartz, Joel Baccarelli, Andrea A eng R01 ES025225/ES/NIEHS NIH HHS/ R01 ES021733/ES/NIEHS NIH HHS/ R01 ES027747/ES/NIEHS NIH HHS/ F31 AG056124/AG/NIA NIH HHS/ R00 ES023450/ES/NIEHS NIH HHS/ P30 ES009089/ES/NIEHS NIH HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Validation Study England Int J Epidemiol. 2019 Dec 1;48(6):1958-1971. doi: 10.1093/ije/dyz082.

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