Am J Epidemiol. 2023 May 5;192(5):800-811. doi: 10.1093/aje/kwad025.
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.
受我们对社会暴露和加速老化的文献综述的启发,这些老化可以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,我们报告了在流行病学文献中处理这些和其他研究中使用其他常见暴露(即体重指数和饮酒)时年龄的 3 种不同方法——1 种不正确,2 种正确。在回顾的 50 篇实证文章中,大多数(n=29;58%)使用了不正确的方法,即分析去趋势的加速老化作为因变量,而不将年龄作为协变量进行控制。相比之下,只有 42%使用了正确的方法,这些方法要么是分析去趋势的加速老化作为因变量,并将年龄作为协变量进行控制(n=16;32%),要么是分析原始的 DNAm 年龄作为因变量,并将年龄作为协变量进行控制(n=5;10%)。与之前使用不正确方法引入的偏差的证明一致,我们提供了模拟分析和其他实证分析,以说明不正确的方法如何导致对零假设的偏差,我们还讨论了对现有研究的影响和最佳实践的建议。