Evidence map›Paper›PMID 26612861›Full record

ArticleNucleic acids research2016

Substantial DNA methylation differences between two major neuronal subtypes in human brain.

Alexey Kozlenkov, Minghui Wang, Panos Roussos, Sergei Rudchenko, Mihaela Barbu, Marina Bibikova, Brandy Klotzle, Andrew J Dwork, Bin Zhang, Yasmin L Hurd and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 110 citations in OpenAlex.

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  11. Epigenetic analyses in forensic medicine: future and challenges.International journal of legal medicine · 2024
    Review
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  13. Article
  14. Review
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12 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

13 authors at 5 institutions in 1 country.

Alexey KozlenkovJames J. Peters VA Medical Center, Bronx, NY 10468, USA The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Minghui WangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Panos RoussosJames J. Peters VA Medical Center, Bronx, NY 10468, USA The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sergei RudchenkoHospital for Special Surgery, New York, NY 10021, USA.
Mihaela BarbuHospital for Special Surgery, New York, NY 10021, USA.
Marina BibikovaIllumina, Inc., San Diego, CA 92122, USA.
Brandy KlotzleIllumina, Inc., San Diego, CA 92122, USA.
Andrew J DworkDepartment of Psychiatry, Columbia University, New York, NY 10032, USA.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yasmin L HurdThe Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Michael WegnerInstitut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.ORCID http://orcid.org/0000-0002-4586-3294
Stella DrachevaJames J. Peters VA Medical Center, Bronx, NY 10468, USA The Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA Stella.Dracheva@mssm.edu.
Icahn School of Medicine at Mount Sinai · USHospital for Special Surgery · USIllumina (United States) · USColumbia University · USNational Center for Biotechnology Information · US

Funding

Comparative Analysis Of Completely Sequenced GenomesZIALM000073 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$43.1M
TRANSGENIC COREP01DA008227 · NIDA · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1993 to 2018
$28.1M
REPRESSIVE HISTONE AND DNA METHYLATION IN RODENT DEPRESSION MODELSP50MH096890 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI TAMMINGA, CAROL A · 2012 to 2021
$20.2M
Higher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2M
The Opioid mesolimbic system in heroin abuseR01DA015446 · NIDA · KAROLINSKA INSTITUTE · PI HURD, YASMIN L. · 2002 to 2018
$7.1M
GABA Epigenomes in AutismR21MH103877 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2014 to 2015
$447k
Molecular Determinants of Individual Differences in Fear Reactivity and RecoveryR21MH097156 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DRACHEVA, STELLA, LEDOUX, JOSEPH E · 2012 to 2013
$389k
Genetic and Molecular Determinants of SuicideI01BX001829 · VA · JAMES J PETERS VA MEDICAL CENTER · PI DRACHEVA, STELLA · 2014 to 2016
–
Dissecting Cis Regulation of Gene Expression in SchizophreniaI01BX002395 · VA · JAMES J PETERS VA MEDICAL CENTER · PI ROUSSOS, PANAGIOTIS · 2014 to 2022
–
BLRD VA I01 BX001829BLRD VA I01 BX002395Intramural NIH HHSNIA NIH HHS R01 AG050986NIDA NIH HHS P01 DA008227NIDA NIH HHS R01 DA015446NIMH NIH HHS P50 MH096890NIMH NIH HHS R21 MH097156NIMH NIH HHS R21 MH103877NIMH NIH HHS R21MH103877
6 · The paper itself

Abstract

The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons--GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.

Indexed as

DNA MethylationEpigenesis, GeneticGenetic LociAdultAutopsyBrain MappingCpG IslandsGABAergic NeuronsGlutamic AcidHumansMaleMicrotomyMiddle AgedNeuronsOrgan SpecificityPrefrontal CortexGlutamic Acid

Identifiers

PMID26612861
PMCPMC4824074
OpenAlexW2327618684

What OpenQuestion holds

Textmetadata
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.