Evidence map›Paper›PMID 31843015›Full record

ArticleClinical epigenetics2019

Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation.

Larissa Haertle, Tobias Müller, Roy Lardenoije, Anna Maierhofer, Marcus Dittrich, Renzo J M Riemens, Samantha Stora, Mathilde Roche, Markus Leber, Steffi Riedel-Heller and 12 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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

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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

22 authors at 11 institutions in 5 countries.

Larissa HaertleInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
Tobias MüllerDepartment of Bioinformatics, Julius Maximilian University, Wuerzburg, Germany.
Roy LardenoijeDepartment of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, the Netherlands.
Anna MaierhoferInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
Marcus DittrichInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
Renzo J M RiemensInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
Samantha StoraInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Mathilde RocheInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Markus LeberDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.
Steffi Riedel-HellerInstitute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103, Leipzig, Germany.
Michael WagnerDepartment of Neurodegeneration and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany.
Martin SchererDepartment of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany.
Aimé RavelInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Clotilde MircherInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Cecile Cieuta-WaltiInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Sophie DurandInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.
Daniel L A van de HoveDepartment of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, the Netherlands.
Per HoffmannInstitute of Human Genetics, University of Bonn, 53127, Bonn, Germany.
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.
Thomas HaafInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
Nady El HajjInstitute of Human Genetics, Julius Maximilian University, Wuerzburg, Germany.
André MégarbanéInstitut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France. andre.megarbane@institutlejeune.org.
Fondation Jérôme-Lejeune · FRUniversity of Bonn · DEHamad bin Khalifa University · QALeipzig University · DEMaastricht University · NLUniversität Hamburg · DEUniversitätsklinikum Würzburg · DEUniversitätsmedizin Göttingen · DEUniversity Hospital of Basel · CHUniversity of Cologne · DEUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTrisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer's disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals. MATERIALS AND

methodsA genome-wide DNA methylation study was performed using Illumina Infinium® MethylationEPIC BeadChips on whole blood DNA of 3 male T21 patients with low IQ, 8 T21 patients with high IQ (4 males and 4 females), and 21 age- and sex-matched control samples (12 males and 9 females) in order to determine whether DNA methylation alterations could help explain variation in cognitive impairment between individuals with T21. In view of the increased risk of developing AD in T21 individuals, we additionally investigated the T21-associated sites in published blood DNA methylation data from the AgeCoDe cohort (German study on Ageing, Cognition, and Dementia). AgeCoDe represents a prospective longitudinal study including non-demented individuals at baseline of which a part develops AD dementia at follow-up.

resultsTwo thousand seven hundred sixteen differentially methylated sites and regions discriminating T21 and healthy individuals were identified. In the T21 high and low IQ comparison, a single CpG located in the promoter of PELI1 was differentially methylated after multiple testing adjustment. For the same contrast, 69 differentially methylated regions were identified. Performing a targeted association analysis for the significant T21-associated CpG sites in the AgeCoDe cohort, we found that 9 showed significant methylation differences related to AD dementia, including one in the ADAM10 gene. This gene has previously been shown to play a role in the prevention of amyloid plaque formation in the brain.

conclusionThe differentially methylated regions may help understand the interaction between methylation alterations and cognitive function. In addition, ADAM10 might be a valuable blood-based biomarker for at least the early detection of AD.

Indexed as

DNA MethylationADAM10 ProteinAdultAlzheimer DiseaseAmyloid Precursor Protein SecretasesCognitionDown SyndromeEarly DiagnosisEpigenesis, GeneticEpigenomicsFemaleGenome-Wide Association StudyGermanyHumansLongitudinal StudiesMaleADAM10 ProteinADAM10 protein, humanAmyloid Precursor Protein SecretasesMembrane ProteinsAlzheimer’s diseaseCognitive functionDNA methylationDown syndromeInfinium Methylation EPIC arraysIntellectual disabilityTrisomy 21

Identifiers

PMID31843015
PMCPMC6916110
OpenAlexW2996257163

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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.