Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: implications and recommendations for best practices

Nancy Krieger*, Jarvis Chen, Christian Testa, Ana V Diez Roux, Kate M Tilling, Sarah H Watkins, Andrew J Simpkin, Matthew J Suderman, George Davey Smith, Immaculata De Vivo, Pamela Waterman, Caroline L Relton

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)

Abstract

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 patterns (DNAm)), we report on three different approaches – 1 incorrect and 2 correct – in the epidemiologic literature on 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 the 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 the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias to the null, and we discuss implications for extant research and recommendations for best practices.
Original languageEnglish
Article numberkwad025
Pages (from-to)800–811
Number of pages12
JournalAmerican Journal of Epidemiology
Volume192
Issue number5
Early online date30 Jan 2023
DOIs
Publication statusPublished - 1 May 2023

Bibliographical note

Funding Information:
This work was funded by the National Institute of Minority Health and Health Disparities, US National Institutes of Health (grant R01MD014304 to N.K. and C.R., as multiple Principal Investigators), with the portions involving ASLPAC being funded by the Medical Research Council and the Wellcome Trust (grant 217065/Z/19/Z) and the University of Bristol (Bristol, United Kingdom) and the portions pertaining to ARIES ( https://clinicaltrials.gov/ct2/show/NCT02581891 ) being funded by the Biotechnology and Biological Sciences Research Council (grants BBI025751/1 and BB/I025263/1). Supplementary funding for generation of the DNA methylation data included in ARIES was obtained from the Medical Research Council, the Economic and Social Research Council, the National Institutes of Health, and other sources. ARIES is maintained under the auspices of the MRC Integrative Epidemiology Unit at the University of Bristol (grants MC_UU_12013/2, MC_UU_12013/8, and MRC_UU_12013/9).

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journalpermissions@oup.com.

Structured keywords

  • Bristol Population Health Science Institute

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