Evidence map›Paper›PMID 24135035›Full record

ArticleHuman molecular genetics2014

A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects.

Joseph L McClay, Karolina A Aberg, Shaunna L Clark, Srilaxmi Nerella, Gaurav Kumar, Lin Y Xie, Alexandra D Hudson, Aki Harada, Christina M Hultman, Patrik K E Magnusson and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 165 citations in OpenAlex.

  1. Review
  2. Article
  3. Frontiers in medicine · 2026
    Article
  4. Article
  5. Article
  6. Accumulation of Epigenetic Noise in the Aging Corneal Epithelium and Its Possible Mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Diagnostics (Basel, Switzerland) · 2024
    Article
  11. Epigenetic analyses in forensic medicine: future and challenges.International journal of legal medicine · 2024
    Review
  12. Complex Regulation of Protocadherin Epigenetics on Aging-Related Brain Health.medRxiv : the preprint server for health sciences · 2024
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

32 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Joseph L McClayCenter for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Karolina A Aberg
Shaunna L Clark
Srilaxmi Nerella
Gaurav Kumar
Lin Y Xie
Alexandra D Hudson
Aki Harada
Christina M Hultman
Patrik K E Magnusson
Patrick F Sullivan
Edwin J C G Van Den Oord
Virginia Commonwealth University · USKarolinska Institutet · SEUniversity of North Carolina at Chapel Hill · US

Funding

A Large-Scale Schizophrenia Association Study in SwedenR01MH077139 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2007 to 2018
$9.9M
Whole genome profiling to detect schizophrenia methylation markersRC2MH089996 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI VAN DEN OORD, EDWIN · 2009 to 2010
$4.5M
Investigating Methylation Patterns Associated with Alcohol Use and AddictionK01AA021266 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI CLARK, SHAUNNA L · 2012 to 2016
$580k
NIAAA NIH HHS K01 AA021266NIMH NIH HHS MH077139NIMH NIH HHS R01 MH077139NIMH NIH HHS RC2MH089996
6 · The paper itself

Abstract

The central importance of epigenetics to the aging process is increasingly being recognized. Here we perform a methylome-wide association study (MWAS) of aging in whole blood DNA from 718 individuals, aged 25-92 years (mean = 55). We sequenced the methyl-CpG-enriched genomic DNA fraction, averaging 67.3 million reads per subject, to obtain methylation measurements for the ∼27 million autosomal CpGs in the human genome. Following extensive quality control, we adaptively combined methylation measures for neighboring, highly-correlated CpGs into 4 344 016 CpG blocks with which we performed association testing. Eleven age-associated differentially methylated regions (DMRs) passed Bonferroni correction (P-value < 1.15 × 10(-8)). Top findings replicated in an independent sample set of 558 subjects using pyrosequencing of bisulfite-converted DNA (min P-value < 10(-30)). To examine biological themes, we selected 70 DMRs with false discovery rate of <0.1. Of these, 42 showed hypomethylation and 28 showed hypermethylation with age. Hypermethylated DMRs were more likely to overlap with CpG islands and shores. Hypomethylated DMRs were more likely to be in regions associated with polycomb/regulatory proteins (e.g. EZH2) or histone modifications H3K27ac, H3K4m1, H3K4m2, H3K4m3 and H3K9ac. Among genes implicated by the top DMRs were protocadherins, homeobox genes, MAPKs and ryanodine receptors. Several of our DMRs are at genes with potential relevance for age-related disease. This study successfully demonstrates the application of next-generation sequencing to MWAS, by interrogating a large proportion of the methylome and returning potentially novel age DMRs, in addition to replicating several loci implicated in previous studies using microarrays.

Indexed as

CpG IslandsDNA MethylationEpigenomicsAdultAgedAged, 80 and overAgingComputational BiologyDNADNA-Binding ProteinsEpigenesis, GeneticFemaleGene Regulatory NetworksGenome-Wide Association StudyHigh-Throughput Nucleotide SequencingHumansDNADNA-Binding ProteinsMBD1 protein, humanTranscription Factors

Identifiers

PMID24135035
PMCPMC3919012
OpenAlexW2162275942

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.