Evidence mapPaperPMID 41315928Full record

ArticleThe journal of headache and pain2025

Epigenome-wide DNA methylation profiling reveals risk genes for migraine and its subtypes.

Mengge Liu, Jian Shang, Minghuan Lei, Wei Wang, Jin Qiao, Xinyu Wang, Qi An, Wenjie Cai, Haolin Wang, Dan Zhu and 2 more

Abstract read
In one paragraph

Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Mengge Liu *Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Jian Shang *Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Minghuan Lei *Department of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Wei WangDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Jin QiaoDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Xinyu WangDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Qi AnDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Wenjie CaiDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Haolin WangDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Dan ZhuDepartment of Radiology, Tianjin Medical University General Hospital Airport Hospital, No. 85, Dongliu Road, Airport Economic Area, Tianjin, 300308, China. zhudan@tmu.edu.cn.
Yanmin PengSchool of Medical Imaging and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University, No. 1, Guangdong Road, Hexi District, Tianjin, 300204, China. pymnn@163.com.
Feng LiuDepartment of Radiology and Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China. fengliu@tmu.edu.cn.

Funding

TianHe Qingsuo Open Research Fund of TSYS in 2022 & NSCCTJ P-THQS-22-PY-No.0004Tianjin Key Medical Discipline Construction Project TJYXZDXK-3-008CTianjin Science and Technology Planning Project 21ZXJBSY00120
6 · The paper itself

Abstract

backgroundMigraine is a highly disabling neurovascular disorder, yet its underlying molecular mechanisms remain incompletely understood. Emerging evidence implicates epigenetic modifications, particularly DNA methylation, in migraine pathophysiology, but whether these changes play a causal role has not been established.

methodsWe integrated large-scale brain and blood methylation quantitative trait loci (mQTL) datasets with genome-wide association study (GWAS) data to investigate the causal role of DNA methylation in migraine and its subtypes. Two-sample Mendelian randomization (MR) was applied to evaluate the effects of cytosine-phosphate-guanine (CpG) methylation on migraine risk. Significant CpG sites were annotated to genes and refined through a multi-step prioritization framework incorporating colocalization, expression QTL (eQTL)-MR, two-step MR, and gene-based association analyses. Functional enrichment, protein-protein interaction, and drug-gene analyses were then performed to explore biological mechanisms and therapeutic potential.

resultsWe identified 169 CpG sites with causal effects on migraine, mapping to 68 genes. Subtype analyses revealed 10 additional genes associated with MA and MO, including three genes specific to MA and one to MO, expanding the total to 72 non-overlapping migraine risk genes. Integrative prioritization highlighted 12 high-confidence genes, among which CFDP1, ICA1L and SERPING1 was supported by all five analytical approaches. Functional characterization indicated significant enrichment in calcitonin-like ligand receptors, axon development and neurovascular regulation, while drug-gene interaction analyses suggested therapeutic potential for targets such as MAPT and CALCA.

conclusionOur findings provide robust evidence that DNA methylation contributes causally to migraine risk and its subtypes, identify genes of biological and therapeutic relevance, and offer novel insights into the epigenetic mechanisms underlying migraine pathophysiology.

Indexed as

DNA MethylationEpigenesis, GeneticEpigenomeGenetic Predisposition to DiseaseMigraine DisordersCpG IslandsGenome-Wide Association StudyHumansMendelian Randomization AnalysisQuantitative Trait LociColocalization analysisDNA methylationGWASMendelian randomizationMigraineMigraine with auraMigraine without aura

Identifiers

PMID41315928
PMCPMC12664279

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.