Evidence map›Paper›PMID 38414347›Full record

ArticleAging cell2024

Epigenome-wide analysis of frailty: Results from two European twin cohorts.

Jonathan K L Mak, Asmus Cosmos Skovgaard, Marianne Nygaard, Laura Kananen, Chandra A Reynolds, Yunzhang Wang, Ralf Kuja-Halkola, Ida K Karlsson, Nancy L Pedersen, Sara Hägg and 2 more

Open access · goldAbstract readTwin Study
In one paragraph

Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% of its field
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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Biomarkers and Clinical Evaluation in the Detection of Frailty.International journal of molecular sciences · 2025
    Review
  8. Review
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 5 countries.

Jonathan K L MakDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-4454-8580
Asmus Cosmos SkovgaardThe Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.
Marianne NygaardThe Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.
Laura KananenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-3742-8927
Chandra A ReynoldsInstitute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA.
Yunzhang WangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ralf Kuja-HalkolaDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ida K KarlssonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-3605-7829
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-2452-1500
Mette SoerensenThe Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.
Juulia JylhäväDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEUniversity of Southern Denmark · DKTampere University · FIUniversity of California, Riverside · US

Funding

TRAJECTORIES OF MORTALITY IN CAENORHABDITIS ELEGANSP01AG008761 · NIA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI YASHIN, ANATOLIY I · 1990 to 2008
$17.5M
GENETIC &ENVIRONMENTAL INFLUENCES--BIOBEHAVIORAL AGINGR01AG010175 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PEDERSEN, NANCY L · 1992 to 2006
$2.8M
GENETIC AND ENVIRONMENTAL INFLUENCES IN BEHAVIORAL AGINGR01AG004563 · NIA · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI MCCLEARN, GERALD E · 1985 to 1988
–
European Union's Seventh Framework Programme FP7/2007-2011Fabrikant Vilhelm Pedersen og Hustrus LegatForskningsrådet för Arbetsliv och Socialvetenskap 2009-0795Forskningsrådet för Arbetsliv och Socialvetenskap 97:0147:1BForskningsrådet om Hälsa, Arbetsliv och VälfärdJuho Vainion Säätiö 202100335Karolinska InstitutetKing Gustaf V and Queen Victoria's Foundation of FreemasonsLoo and Hans Osterman Foundation for Medical ResearchMacArthur Foundation Research Network on Successful AgingNIA NIH HHS P01 AG008761NIA NIH HHS P01 AG08761NIA NIH HHS R01 AG010175NIH HHS AG04563NIH HHS AG10175Sigrid Juséliuksen SäätiöTampereen TuberkuloosisäätiöVetenskapsrådet 2018-02077Vetenskapsrådet 2019-01272Vetenskapsrådet 2020-06101Vetenskapsrådet 825-2007-7460Vetenskapsrådet 825-2009-6141Wellcome Trust 220032Yrjö Jahnssonin Säätiö 20217416
6 · The paper itself

Abstract

Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.

Indexed as

DNA MethylationEpigenomeFrailtyAgedAged, 80 and overAgingCohort StudiesCpG IslandsEpigenesis, GeneticFemaleGenome-Wide Association StudyHumansLongitudinal StudiesMaleagingDNA methylationepigeneticsfrailty

Identifiers

PMID38414347
PMCPMC11166364
OpenAlexW4392237293

What OpenQuestion holds

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Registered trials

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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.