Evidence map›Paper›PMID 35027166›Full record

ArticleBiological psychiatry2022

Contribution of Age, Brain Region, Mood Disorder Pathology, and Interindividual Factors on the Methylome of Human Microglia.

Lot D de Witte, Zhaoyu Wang, Gijsje L J L Snijders, Natalia Mendelev, Qingkun Liu, Marjolein A M Sneeboer, Marco P M Boks, Yongchao Ge, Fatemeh Haghighi

Open access · hybridAbstract read
In one paragraph

Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  6. Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
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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

9 authors at 3 institutions in 2 countries.

Lot D de WitteMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
Zhaoyu WangMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
Gijsje L J L SnijdersMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
Natalia MendelevMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
Qingkun LiuMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
Marjolein A M SneeboerDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, University Medical Center Utrecht, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands; Department of Translational Neuroscience, University Medical Center Utrecht, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
Marco P M BoksDepartment of Psychiatry, University Medical Center Utrecht, UMC Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
Yongchao GeDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York.
Fatemeh HaghighiMental Illness Research, Education and Clinical Center, James J Peters VA Medical Center, Bronx, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: fatemeh.haghighi@mssm.edu.
James J. Peters VA Medical Center · USUtrecht University · NLIcahn School of Medicine at Mount Sinai · US

Funding

CSR&D Research Career Scientist Award ApplicationIK6CX002074 · VA · JAMES J PETERS VA MEDICAL CENTER · PI HAGHIGHI, FATEMEH G · 2020 to 2025
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BLRD VA I01 BX003794CSRD VA I01 CX001395CSRD VA I01 CX001728CSRD VA IK6 CX002074RRD VA I01 RX001705
6 · The paper itself

Abstract

backgroundTranscriptome studies have revealed age-, disease-, and region-associated microglial phenotypes reflecting changes in microglial function during development, aging, central nervous system homeostasis, and pathology. The molecular mechanisms that contribute to these transcriptomic changes are largely unknown. The aim of this study was to characterize the DNA methylation landscape of human microglia and the factors that contribute to variations in the microglia methylome. We hypothesized that both age and brain region would have a large impact on DNA methylation in microglia.

methodsMicroglia from postmortem brain tissue of four different brain regions of 22 donors, encompassing 1 patient with schizophrenia, 13 patients with mood disorder pathology, and 8 control subjects, were isolated and assayed using a genome-wide methylation array.

resultsWe found that human microglial cells have a methylation profile distinct from bulk brain tissue and neurons, and age explained a considerable part of the variation. Additionally, we showed that interindividual factors had a much larger effect on the methylation landscape of microglia than brain region, which was also seen at the transcriptome level. In our exploratory analysis, we found various differentially methylated regions that were related to disease status (mood disorder vs. control). This included differentially methylated regions that are linked to gene expression in microglia, as well as to myeloid cell function or neuropsychiatric disorders.

conclusionsAlthough based on relatively small samples, these findings suggest that the methylation profile of microglia is responsive to interindividual variations and thereby plays an important role in the heterogeneity of microglia observed at the transcriptome level.

Indexed as

EpigenomeMicrogliaBrainDNA MethylationHumansMood DisordersTranscriptomeBipolar disorderBrain regionDepressionMethylationMicrogliaTranscriptome

Identifiers

PMID35027166
PMCPMC11181298
OpenAlexW3208640347

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.