Evidence map›Paper›PMID 30898171›Full record

ArticleClinical epigenetics2019

Parallel profiling of DNA methylation and hydroxymethylation highlights neuropathology-associated epigenetic variation in Alzheimer's disease.

Adam R Smith, Rebecca G Smith, Ehsan Pishva, Eilis Hannon, Janou A Y Roubroeks, Joe Burrage, Claire Troakes, Safa Al-Sarraj, Carolyn Sloan, Jonathan Mill and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 8 pooled it
6.6field-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

65 citing papers in PubMed, 8 syntheses or guidelines pooled it, 129 citations in OpenAlex.

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  14. Delineating blood DNA methylation biomarkers for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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  19. Article
  20. DNA Methylation in Alzheimer's Disease.Current topics in behavioral neurosciences · 2025
    Review

5 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 4 institutions in 4 countries.

Adam R SmithCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Rebecca G SmithCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Ehsan PishvaCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Eilis HannonCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Janou A Y RoubroeksCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Joe BurrageCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Claire TroakesInstitute of Psychiatry, King's College London, London, UK.
Safa Al-SarrajInstitute of Psychiatry, King's College London, London, UK.
Carolyn SloanNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Jonathan MillCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK.
Daniel L van den HoveDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.
Katie LunnonCollege of Medicine and Health, University of Exeter Medical School, Exeter University, RILD Building Level 4, Royal Devon and Exeter Hospital, Barrack Rd, Exeter, EX2 5DW, UK. k.lunnon@exeter.ac.uk.ORCID 0000-0001-7570-6065
University of Exeter · GBKing's College London · GBUniversity of Oxford · GBUniversity of Würzburg · DE

Funding

Medical Research Council MR/L016397/1Medical Research Council MR/N027973/1
6 · The paper itself

Abstract

backgroundAlzheimer's disease is a progressive neurodegenerative disorder that is hypothesized to involve epigenetic dysfunction. Previous studies of DNA modifications in Alzheimer's disease have been unable to distinguish between DNA methylation and DNA hydroxymethylation. DNA hydroxymethylation has been shown to be enriched in the human brain, although its role in Alzheimer's disease has not yet been fully explored. Here, we utilize oxidative bisulfite conversion, in conjunction with the Illumina Infinium Human Methylation 450K microarray, to identify neuropathology-associated differential DNA methylation and DNA hydroxymethylation in the entorhinal cortex.

resultsWe identified one experiment-wide significant differentially methylated position residing in the WNT5B gene. Next, we investigated pathology-associated regions consisting of multiple adjacent loci. We identified one significant differentially hydroxymethylated region consisting of four probes spanning 104 bases in the FBXL16 gene. We also identified two significant differentially methylated regions: one consisting of two probes in a 93 base-pair region in the ANK1 gene and the other consisting of six probes in a 99-base pair region in the ARID5B gene. We also highlighted three regions that show alterations in unmodified cytosine: two probes in a 39-base pair region of ALLC, two probes in a 69-base pair region in JAG2, and the same six probes in ARID5B that were differentially methylated. Finally, we replicated significant ANK1 disease-associated hypermethylation and hypohydroxymethylation patterns across eight CpG sites in an extended 118-base pair region in an independent cohort using oxidative-bisulfite pyrosequencing.

conclusionsOur study represents the first epigenome-wide association study of both DNA methylation and hydroxymethylation in Alzheimer's disease entorhinal cortex. We demonstrate that previous estimates of DNA hypermethylation in ANK1 in Alzheimer's disease were underestimates as it is confounded by hypohydroxymethylation.

Indexed as

DNA MethylationGenetic VariationAgedAged, 80 and overAlzheimer DiseaseAnkyrinsDNA-Binding ProteinsEntorhinal CortexEpigenesis, GeneticF-Box ProteinsFemaleHumansMaleOligonucleotide Array Sequence AnalysisTranscription FactorsWhole Genome SequencingANK1 protein, humanAnkyrinsARID5B protein, humanDNA-Binding ProteinsF-Box ProteinsTranscription FactorsWNT5B protein, humanWnt ProteinsAlzheimer’s disease (AD)Ankyrin 1 (ANK1)BrainDNA hydroxymethylation (5hmC)DNA methylation (5mC)Entorhinal cortex (EC)EpigeneticsEpigenome-wide association study (EWAS)Illumina Infinium Human Methylation 450K microarray (450K array)

Identifiers

PMID30898171
PMCPMC6429761
OpenAlexW2938014360

What OpenQuestion holds

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LicenceCC BY
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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.