Evidence map›Paper›PMID 29550519›Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2018

Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology.

Rebecca G Smith, Eilis Hannon, Philip L De Jager, Lori Chibnik, Simon J Lott, Daniel Condliffe, Adam R Smith, Vahram Haroutunian, Claire Troakes, Safa Al-Sarraj and 6 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 11 pooled it
10.2field-weighted citation impact, top 1% 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

119 citing papers in PubMed, 11 syntheses or guidelines pooled it, 206 citations in OpenAlex.

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  15. Blood DNA Methylation Predicts Long-Term Risk of Dementia in Prospective Cohorts.medRxiv : the preprint server for health sciences · 2026
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59 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

16 authors at 11 institutions in 2 countries.

Rebecca G SmithInstitute of Clinical and Biomedical Science, University of Exeter Medical School, RILD Building, Royal Devon & Exeter Hospital Campus, Exeter, Devon, UK.
Eilis HannonInstitute of Clinical and Biomedical Science, University of Exeter Medical School, RILD Building, Royal Devon & Exeter Hospital Campus, Exeter, Devon, UK.
Philip L De JagerProgram in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Neurology, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
Lori ChibnikProgram in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Simon J LottInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Daniel CondliffeQueen Mary University of London, London, UK.
Adam R SmithInstitute of Clinical and Biomedical Science, University of Exeter Medical School, RILD Building, Royal Devon & Exeter Hospital Campus, Exeter, Devon, UK.
Vahram HaroutunianDepartment of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; JJ Peters VA Medical Center, Bronx, NY, USA.
Claire TroakesInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Safa Al-SarrajInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
John PowellInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Simon LovestoneDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Leonard SchalkwykUniversity of Essex, Colchester, UK.
Jonathan MillInstitute of Clinical and Biomedical Science, University of Exeter Medical School, RILD Building, Royal Devon & Exeter Hospital Campus, Exeter, Devon, UK. Electronic address: j.mill@exeter.ac.uk.
Katie LunnonInstitute of Clinical and Biomedical Science, University of Exeter Medical School, RILD Building, Royal Devon & Exeter Hospital Campus, Exeter, Devon, UK. Electronic address: k.lunnon@exeter.ac.uk.
King's College London · GBExeter Hospital · USBrigham and Women's Hospital · USColumbia University Irving Medical Center · USIcahn School of Medicine at Mount Sinai · USQueen Mary University of London · GBRoyal Devon and Exeter Hospital · GBRush University Medical Center · USUniversity of Essex · GBUniversity of Exeter · GBWarneford Hospital · GB

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GROSSMAN, HILLEL · 1985 to 2019
$37.9M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
QUANTITATIVE ANALYSIS OF MICROVASCULAR CHANGES IN THE AGING BRAINP01AG002219 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HAROUTUNIAN, VAHRAM · 1985 to 2009
$19.2M
Production sequencing of reference human epigenomesU01ES017155 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN, MEISSNER, ALEXANDER · 2008 to 2012
$15.4M
Mayo Clinic Center for Translational Science ActivitiesKL2RR024151 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$15.3M
Exploring the Role of the Brain Epigenome: Cognitive Decline and Life ExperiencesRF1AG036042 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2016 to 2016
$5.5M
Exploring the Role of the Brain Epigenome: Cognitive Decline and Life ExperiencesR01AG036042 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2009 to 2013
$4.1M
Cortico-thalamic Glutamate/GABA mRNA in schizophreniaR01MH064673 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HAROUTUNIAN, VAHRAM · 2003 to 2012
$3.4M
PLASMA A BETA AS A SURROGATE GENETIC MARKER FOR LOADR01AG018023 · NIA · MAYO CLINIC JACKSONVILLE · PI YOUNKIN, STEVEN G · 2001 to 2012
$3.3M
Medical Research Council MR/L016397/1NCRR NIH HHS KL2 RR024151NIA NIH HHS K25 AG041906NIA NIH HHS P01 AG002219NIA NIH HHS P30 AG010161NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036039NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG036042NIEHS NIH HHS U01 ES017155NIMH NIH HHS R01 MH064673
6 · The paper itself

Abstract

introductionAlzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain.

methodsWe performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740).

resultsWe identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10 DISCUSSION: We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation.

Indexed as

DNA MethylationAlzheimer DiseaseCpG IslandsEpigenesis, GeneticGenetic Predisposition to DiseaseGenome-Wide Association StudyHomeodomain ProteinsMultigene FamilyPrefrontal CortexTemporal LobeHomeodomain ProteinsHoxA proteinAlzheimer's disease (AD)Braak stageDNA methylationEpigeneticsEpigenome-wide association study (EWAS)HOXAIllumina Infinium 450K BeadChip (450K array)Meta-analysisNeuropathologyPrefrontal cortex (PFC)Superior temporal gyrus (STG)

Identifiers

PMID29550519
PMCPMC6438205
OpenAlexW2789414284

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LicenceCC BY-NC-ND
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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.