Evidence mapPaperPMID 40394501Full record

ArticleThe journal of headache and pain2025

Genetic influence of the brain imaging phenotypes, brain and cerebrospinal fluid metabolites and brain genes on migraine subtypes: a Mendelian randomization and multi-omics study.

Ping-An Zhang, Jie-Lin Wang, Mei-Hua Dong, Xiang-Chun Huang, Nai-Jian Li, Run-Dong Qin, Jing Li

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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 5 papers.

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0cells of the map it votes in
5citing 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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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  3. Integrative Transcriptomic and Genetic Analysis PrioritizesClinical, cosmetic and investigational dermatology · 2026
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4 · The record

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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

7 authors.

Ping-An Zhang *Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong, 510120, China.
Jie-Lin Wang *Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Mei-Hua Dong *Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong, 510120, China.
Xiang-Chun HuangDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Nai-Jian LiDepartment of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong, 510120, China. naijian@126.com.
Run-Dong QinDepartment of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong, 510120, China. 407276157@qq.com.
Jing LiDepartment of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Yuexiu District, Guangzhou, Guangdong, 510120, China. jingli1016@vip.163.com.

Funding

Guangzhou Municipal Science and Technology Project 202102010011National Natural Science Foundation of China 82161138020National Natural Science Foundation of China U1801286Zhongnanshan Medical Foundation of Guangdong Province ZNSA-2020003
6 · The paper itself

Abstract

backgroundMigraine is a complex neurological disorder with high prevalence but unclear pathogenesis. Numerous studies have suggested that migraine is associated with alterations in brain imaging phenotypes (BIPs) and dysregulation of cerebrospinal fluid (CSF) and brain metabolism; however, causal evidence remains limited. Mendelian randomization (MR) offers a powerful approach for inferring causality using genetic instruments.

methodsFirstly, we conducted linkage disequilibrium score regression (LDSC) to evaluate genetic correlations between migraine, including the migraine with aura (MA) and migraine without aura (MO) subtypes, and BIPs, CSF, and brain metabolites. Traits that showed genetic correlations with migraine, MA, or MO were retained for subsequent MR analysis with the corresponding migraine phenotype. Traits showing significant correlations were analyzed using bidirectional two-sample MR (TSMR), followed by two-step TSMR to identify cross-omics mediation effects. Additionally, We also applied summary-data-based MR (SMR) to detect brain-region-specific genes with potential causal effects. Enrichment analyses (KEGG, GO, PPI, transcription factor, and miRNA networks) were conducted to further explore underlying mechanisms.

resultsLDSC identified significant genetic correlations with 73 BIPs and 40 metabolites for overall migraine, 71 BIPs and 37 metabolites for MA, and 49 BIPs and 62 metabolites for MO. Enrichment analysis revealed that genetically associated metabolites were predominantly involved in amino acid metabolic pathways. TSMR identified 6 BIPs and 2 metabolites causally linked to overall migraine, 3 BIPs and 3 metabolites to MA, and 2 BIPs and 5 metabolites to MO. Most migraine-related BIPs mapped to the parietal lobe. Reverse MR analysis showed that overall migraine causally influenced 4 BIPs and 3 metabolites, while MA and MO affected 1 BIP and 1 metabolite, and 3 BIPs and 1 metabolite, respectively. Mediation analysis revealed five significant mediation pathways were identified. SMR analysis identified FAM83B and CIB2 consistently showing inhibitory effects across most regions. Enrichment analysis showed that these genes were predominantly involved in immune activation and cell adhesion.

conclusionsOur study integrates cross-omics analyses to investigate the causal links between brain structure, metabolic alterations, gene expression, and migraine including its MA and MO subtypes. These findings provide novel insights into the pathophysiological mechanisms and potential targets for intervention across migraine subtypes.

Indexed as

BrainMigraine DisordersMigraine with AuraMigraine without AuraHumansLinkage DisequilibriumMagnetic Resonance ImagingMendelian Randomization AnalysisMultiomicsNeuroimagingPhenotypeBrain and cerebrospinal fluid metabolitesBrain imaging phenotypesGenome-wide associationMendelian randomizationMigraineMulti-omics

Identifiers

PMID40394501
PMCPMC12090607

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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 Socratic graph.