Evidence map›Paper›PMID 24603599›Full record

ArticlePLoS genetics2014

An epigenetic signature in peripheral blood associated with the haplotype on 17q21.31, a risk factor for neurodegenerative tauopathy.

Yun Li, Jason A Chen, Renee L Sears, Fuying Gao, Eric D Klein, Anna Karydas, Michael D Geschwind, Howard J Rosen, Adam L Boxer, Weilong Guo and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

57 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Blood DNA methylation as a potential biomarker of dementia: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018
    Pooled it
  3. Review
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  10. DNA methylation as a contributor to dysregulation ofbioRxiv : the preprint server for biology · 2025
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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

15 authors.

Yun LiDepartment of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Jason A ChenInterdepartmental Program in Bioinformatics, University of California Los Angeles, Los Angeles, California, United States of America.
Renee L SearsProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Fuying GaoDepartment of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Eric D KleinProgram in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Anna KarydasMemory and Aging Center/Sandler Neurosciences Center, University of California San Francisco, San Francisco, California, United States of America.
Michael D GeschwindMemory and Aging Center/Sandler Neurosciences Center, University of California San Francisco, San Francisco, California, United States of America.
Howard J RosenMemory and Aging Center/Sandler Neurosciences Center, University of California San Francisco, San Francisco, California, United States of America.
Adam L BoxerMemory and Aging Center/Sandler Neurosciences Center, University of California San Francisco, San Francisco, California, United States of America.
Weilong GuoBioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing, China; Department of Molecular, Cell and Developmental Biology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Steve HorvathDepartments of Biostatistics and Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Bruce L MillerMemory and Aging Center/Sandler Neurosciences Center, University of California San Francisco, San Francisco, California, United States of America.
Daniel H GeschwindDepartment of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Giovanni CoppolaDepartment of Psychiatry and Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
The Four Repeat Tauopathy Neuroimaging InitiativeR01AG038791 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L. · 2010 to 2020
$18.1M
The Frontotemporal Lobar Degeneration Neuroimaging InitiativeR01AG032306 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSEN, HOWARD J · 2009 to 2013
$10.0M
Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
Predicting progression of human prion diseaseR01AG031189 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GESCHWIND, MICHAEL D · 2008 to 2017
$5.7M
Novel Genetic Risk Factors for Alzheimer's Disease (AD) & Frontotemporal DementiaR01AG026938 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2005 to 2009
$2.5M
Eye Movement Control in Normal Elderly and MCIR01AG031278 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOXER, ADAM L. · 2009 to 2013
$1.2M
Genetic, Genomic, and Imaging Biomarkers in Degenerative DementiaRC1AG035610 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2010
$910k
Genetic Determinants of TauopathiesF31NS084556 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JASON ANDREW · 2013 to 2015
$80k
NIA NIH HHS AG031189NIA NIH HHS AG031278NIA NIH HHS AG032306NIA NIH HHS AG038791NIA NIH HHS P01 AG019724NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG026938NIA NIH HHS R01 AG031189NIA NIH HHS R01 AG031278NIA NIH HHS R01 AG032306NIA NIH HHS R01 AG038791NIA NIH HHS RC1 AG035610NIA NIH HHS RC1AG035610NIGMS NIH HHS T32 GM008042NINDS NIH HHS F31 NS084556NINDS NIH HHS P30 NS062691NINDS NIH HHS P30NS062691
6 · The paper itself

Abstract

Little is known about how changes in DNA methylation mediate risk for human diseases including dementia. Analysis of genome-wide methylation patterns in patients with two forms of tau-related dementia--progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)--revealed significant differentially methylated probes (DMPs) in patients versus unaffected controls. Remarkably, DMPs in PSP were clustered within the 17q21.31 region, previously known to harbor the major genetic risk factor for PSP. We identified and replicated a dose-dependent effect of the risk-associated H1 haplotype on methylation levels within the region in blood and brain. These data reveal that the H1 haplotype increases risk for tauopathy via differential methylation at that locus, indicating a mediating role for methylation in dementia pathophysiology.

Indexed as

Epigenesis, GeneticBrainChromosomes, Human, Pair 17DNA MethylationFrontotemporal DementiaGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHumansNeurodegenerative DiseasesRisk FactorsSupranuclear Palsy, ProgressiveTauopathiestau ProteinsMAPT protein, humantau Proteins

Identifiers

PMID24603599
PMCPMC3945475

What OpenQuestion holds

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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.