Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: Implications and Recommendations for Best Practices.

Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: Implications and Recommendations for Best Practices.
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DOI:
10.1093/aje/kwad025
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发表时间:
2023-05-05
影响因子:
5
通讯作者:
--
中科院分区:
医学2区
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--
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出于我们对社会暴露和加速衰老进行文献综述的动机,通过越来越多的表观遗传“时钟”(通过DNA甲基化(DNAm)模式估计年龄)来衡量,我们报告了流行病学文献中的3种不同方法-1种不正确,2种正确-在这些和其他研究中使用其他常见暴露(即,身体质量指数和酒精消费)。在回顾的50篇经验性文章中,大多数(n = 29; 58%)使用了不正确的加速老化分析方法,将年龄作为结果排除趋势,并且未将年龄作为协变量进行控制。相比之下,只有42%的人使用了正确的方法,要么分析加速老化,年龄作为结果,年龄作为协变量(n = 16; 32%),要么分析原始DNA,年龄作为结果,年龄作为协变量(n = 5; 10%)。在雅阁与先前的示范使用不正确的方法引入的偏见,我们提供模拟分析和额外的实证分析,以说明如何不正确的方法可能会导致偏向零,我们讨论了现存的研究和建议的最佳实践的影响。
Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic “clocks” (which estimate age via DNA methylation (DNAm) patterns), we report on 3 different approaches in the epidemiologic literature—1 incorrect and 2 correct—on the treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%) or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introduced by use of the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias towards the null, and we discuss implications for extant research and recommendations for best practices.
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