Evidence map›Paper›PMID 25129077›Full record

ArticleNature neuroscience2014

Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.

Katie Lunnon, Rebecca Smith, Eilis Hannon, Philip L De Jager, Gyan Srivastava, Manuela Volta, Claire Troakes, Safa Al-Sarraj, Joe Burrage, Ruby Macdonald and 11 more

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

Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 355 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
355citing papers in PubMed, 16 pooled it
21.5field-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

355 citing papers in PubMed, 16 syntheses or guidelines pooled it, 607 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 2 countries.

Katie LunnonUniversity of Exeter Medical School, Exeter University, Exeter, UK.
Rebecca SmithInstitute of Psychiatry, King's College London, London, UK.
Eilis HannonUniversity of Exeter Medical School, Exeter University, Exeter, UK.
Philip L De Jager1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, USA.
Gyan Srivastava1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, USA.
Manuela VoltaInstitute of Psychiatry, King's College London, London, UK.
Claire TroakesInstitute of Psychiatry, King's College London, London, UK.
Safa Al-SarrajInstitute of Psychiatry, King's College London, London, UK.
Joe BurrageUniversity of Exeter Medical School, Exeter University, Exeter, UK.
Ruby MacdonaldUniversity of Exeter Medical School, Exeter University, Exeter, UK.
Daniel CondliffeInstitute of Psychiatry, King's College London, London, UK.
Lorna W HarriesUniversity of Exeter Medical School, Exeter University, Exeter, UK.
Pavel KatselDepartment of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA.
Vahram Haroutunian1] Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA. [2] Department of Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, USA. [3] JJ Peters Virginia Medical Center, Bronx, New York, USA.
Zachary Kaminsky1] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Catharine JoachimDepartment of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
John PowellInstitute of Psychiatry, King's College London, London, UK.
Simon Lovestone1] Institute of Psychiatry, King's College London, London, UK. [2] Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Leonard C Schalkwyk1] Institute of Psychiatry, King's College London, London, UK. [2].
Jonathan Mill1] University of Exeter Medical School, Exeter University, Exeter, UK. [2] Institute of Psychiatry, King's College London, London, UK. [3].
King's College London · GBUniversity of Exeter · GBBrigham and Women's Hospital · USIcahn School of Medicine at Mount Sinai · USJohn Radcliffe Hospital · GBJohns Hopkins University · USRush University Medical Center · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 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 SCHIMMING, CORBETT · 1985 to 2019
$37.9M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 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 G1100695Medical Research Council MR/L022656/1NCRR NIH HHS KL2 RR024151NIA NIH HHS AG02219NIA NIH HHS AG05138NIA NIH HHS K25 AG041906NIA NIH HHS K25 AG041906-01NIA NIH HHS P01 AG002219NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG10161NIA 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 R01AG036836NIA NIH HHS R01 AG15819NIA NIH HHS R01 AG17917NIA NIH HHS R01 AG18023NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG036042NIEHS NIH HHS U01 ES017155NIMH NIH HHS MH064673NIMH NIH HHS R01 MH064673
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAnkyrinsCerebral CortexDNA MethylationEntorhinal CortexEpigenesis, GeneticFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPrefrontal CortexTemporal LobeTranscriptomeANK1 protein, humanAnkyrins

Identifiers

PMID25129077
PMCPMC4410018
OpenAlexW1991244004

What OpenQuestion holds

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Read underepoch 390

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.