Evidence map›Paper›PMID 37696874›Full record

ArticleMolecular psychiatry2023

A higher dysregulation burden of brain DNA methylation in female patients implicated in the sex bias of Schizophrenia.

Jiaqi Zhou, Yan Xia, Miao Li, Yu Chen, Jiacheng Dai, Chunyu Liu, Chao Chen

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Effects of positive mGlu5 modulation on DJournal of psychopharmacology (Oxford, England) · 2025
    Article
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Jiaqi ZhouCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
Yan XiaDepartment of Medicine, Harvard Medical School, Boston, MA, 02114, USA. Yxia@broadinsitute.org.
Miao LiCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
Yu ChenCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
Jiacheng DaiCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
Chunyu LiuCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China. LiuCh@upstate.edu.ORCID 0000-0002-5986-4415
Chao ChenCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and the Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China. chenchao@sklmg.edu.cn.ORCID 0000-0002-5114-2282
Central South University · CNBroad Institute · US

Funding

2/2-Discovery and validation of neuronal enhancers associated with the development of psychiatric disordersU01MH116489 · NIMH · UNIVERSITY OF CHICAGO · PI GAYNOR, SOPHIA, GESCHWIND, DANIEL H · 2018 to 2022
$4.5M
Gene Expression Regulation in Brains of East Asian, African, and European Descent Explains Schizophrenia GWAS in Diverse Populations.R01MH126459 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI Chunyu Liu · 2022 to 2026
$3.7M
1/2 Measuring translational dynamics and the proteome to identify potential brain biomarkers for psychiatric diseaseR01MH110920 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI LIU, CHUNYU · 2016 to 2019
$2.0M
1/3 High-resolution mapping of cell type-specific DNA (hydroxy)methylation in the human brain during postnatal development and in psychiatric disease.U01MH122591 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI LIU, CHUNYU · 2020 to 2022
$483k
1/3 High-resolution mapping of cell type-specific DNA (hydroxy)methylation in the human brain during postnatal development and in psychiatric disease.R01MH122591 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI LIU, CHUNYU · 2023 to 2024
$306k
NIMH NIH HHS R01 MH110920NIMH NIH HHS R01 MH122591NIMH NIH HHS R01 MH126459NIMH NIH HHS U01 MH116489NIMH NIH HHS U01 MH122591
6 · The paper itself

Abstract

Sex differences are pervasive in schizophrenia (SCZ), but the extent and magnitude of DNA methylation (DNAm) changes underlying these differences remain uncharacterized. In this study, sex-stratified differential DNAm analysis was performed in postmortem brain samples from 117 SCZ and 137 controls, partitioned into discovery and replication datasets. Three differentially methylated positions (DMPs) were identified (adj.p < 0.05) in females and 29 DMPs in males without overlap between them. Over 81% of these sex-stratified DMPs were directionally consistent between sexes but with different effect sizes. Females experienced larger magnitude of DNAm changes and more DMPs (based on data of equal sample size) than males, contributing to a higher dysregulation burden of DNAm in females SCZ. Additionally, despite similar proportions of female-related DMPs (fDMPs, 8%) being under genetic control compared with males (10%), significant enrichment of DMP-related single nucleotide polymorphisms (SNPs) in signals of genome-wide association studies was identified only in fDMPs. One DMP in each sex connected the SNPs and gene expression of CALHM1 in females and CCDC149 in males. PPI subnetworks revealed that both female- and male-related differential DNAm interacted with synapse-related dysregulation. Immune-related pathways were unique for females and neuron-related pathways were associated with males. This study reveals remarkable quantitative differences in DNAm-related sexual dimorphism in SCZ and that females have a higher dysregulation burden of SCZ-associated DNAm than males.

Indexed as

DNA MethylationSchizophreniaBrainEpigenesis, GeneticFemaleGenome-Wide Association StudyHumansMaleSexism

Identifiers

PMID37696874
PMCPMC10925554
OpenAlexW4386618255

What OpenQuestion holds

Textmetadata
LicenceTDM
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.