Evidence map›Paper›PMID 39707425›Full record

ArticleClinical epigenetics2024

Maximizing insights from longitudinal epigenetic age data: simulations, applications, and practical guidance.

Anna Großbach, Matthew J Suderman, Anke Hüls, Alexandre A Lussier, Andrew D A C Smith, Esther Walton, Erin C Dunn, Andrew J Simpkin

Abstract read
In one paragraph

Article in Clinical epigenetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Anna GroßbachSchool of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland. anna.grossbach@universityofgalway.ie.
Matthew J SudermanMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Anke HülsDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Alexandre A LussierPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Andrew D A C SmithMathematics and Statistics Research Group, University of the West of England, Bristol, UK.
Esther WaltonDepartment of Psychology, University of Bath, Bath, UK.
Erin C DunnPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Andrew J SimpkinSchool of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland.

Funding

IMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related DementiasU01AG088425 · NIA · EMORY UNIVERSITY · PI Anke Huels, Donghai Liang · 2024 to 2026
$6.8M
Childhood adversity, DNA methylation, and risk for depression: A longitudinal study of sensitive periods in developmentR01MH113930 · NIMH · PURDUE UNIVERSITY · PI Erin Cathleen Dunn · 2017 to 2026
$6.6M
EU Horizon 2020 research and innovation programme 848158EU Horizon 2020 research and innovation programme H2020-MSCA-COFUND-2019- 945385NIA NIH HHS U01 AG088425NIMH NIH HHS R01 MH113930NIMH NIH HHS R01MH113930Science Foundation Ireland 18/CRT/6214UK Research and Innovation EP/Y015037/1
6 · The paper itself

Abstract

backgroundEpigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional, using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (1) their choice of model; (2) the primary outcome (EA vs. EAA); and (3) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA.

resultsOur simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered advanced GrimAge in individuals assigned male at birth that decelerates over time.

conclusionOur results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.

Indexed as

AgingDNA MethylationEpigenesis, GeneticBirth WeightComputer SimulationCpG IslandsEpigenomicsFemaleHumansLongitudinal StudiesMaleAccelerated agingALSPACDNA methylationEpigenetic ageLongitudinal studies

Identifiers

PMID39707425
PMCPMC11662605

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.