Evidence map›Paper›PMID 41959448›Full record

ArticlebioRxiv : the preprint server for biology2026

Distinct cellular DNA methylation mechanisms underlie common and rare genetic risk for brain disorders.

Jiyun Zhou, Cuining Liu, Xiaoming Liu, Yuan Zhang, Yu Wei, Joo Heon Shin, Brady Maher, Chunyu Liu, Chongyuan Luo, Kai Wang and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Jiyun ZhouLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21287, USA.
Cuining LiuDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Xiaoming LiuUSF Genomics & College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, FL 33612, USA.ORCID 0000-0001-8285-5528
Yuan ZhangRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, PA 19104, USA.
Yu WeiDepartment of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Joo Heon ShinLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21287, USA.
Brady MaherLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21287, USA.
Chunyu LiuDepartment of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.ORCID 0000-0002-5986-4415
Chongyuan LuoDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Kai WangRaymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, PA 19104, USA.ORCID 0000-0002-5585-982X
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21287, USA.
Shizhong HanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21287, USA.ORCID 0000-0002-5114-6742

Funding

Functional methylomics approaches for schizophrenia in the frontal cortex and hippocampusR01MH112751 · NIMH · LIEBER INSTITUTE, INC. · PI HAN, SHIZHONG · 2017 to 2021
$3.4M
Novel bioinformatics methods to detect DNA and RNA modifications using Nanopore long-read sequencingR01HG013359 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kai Wang · 2023 to 2026
$2.8M
Integrative approaches to identification and interpretation of genes underlying psychiatric disordersR01MH121394 · NIMH · LIEBER INSTITUTE, INC. · PI HAN, SHIZHONG · 2020 to 2023
$2.4M
NHGRI NIH HHS R01 HG013359NIMH NIH HHS R01 MH112751NIMH NIH HHS R01 MH121394
6 · The paper itself

Abstract

Noncoding genetic variation contributes to brain disorder risk, but the mechanisms through which it acts in specific brain cell types remain unclear. DNA methylation (DNAm), a highly cell type-specific regulatory layer in the brain, may mediate noncoding genetic risk, yet whether methylation at CG (mCG) and neuron-enriched non-CG (mCH) dinucleotides contribute differently to that risk remains unknown. Here we develop a deep learning framework that predicts DNAm from DNA sequence and estimates variant effects across 186 brain cell subtypes in both mCG and mCH, leveraging single-nucleus DNAm profiles from 46 brain regions. The models reveal distinct transcription factor (TF) programs underlying the two methylation contexts, with mCH-associated TFs showing stronger evolutionary constraint. Predicted variant effects agree closely with cell type-matched mQTLs in both direction and magnitude. Common variants predicted to affect mCG, particularly in excitatory neurons, show substantially greater heritability enrichment for brain-related traits than variants affecting mCH. By contrast, noncoding

Identifiers

PMID41959448
PMCPMC13060888

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.