ArticleThe journal of headache and pain2024
Causal relationships between cortical brain structural alterations and migraine subtypes: a bidirectional Mendelian randomization study of 2,347 neuroimaging phenotypes.
Article in The journal of headache and pain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Powering the mind: deciphering the shared genetic architecture between mitochondrial DNA copy number and major psychiatric disorders.Molecular psychiatry · 2026Article
- Epigenome-wide DNA methylation profiling reveals risk genes for migraine and its subtypes.The journal of headache and pain · 2025Article
- Genetic underpinnings and causal effects of brain structure and function on chronic pain intensity.Nature communications · 2025Article
- Causal Relationship Between Inflammatory Bowel Disease and Neuropsychiatric Disorders: A Bidirectional Mendelian Randomization Study.Brain and behavior · 2025Article
- 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.The journal of headache and pain · 2025Article
- Reduced Cortical Surface Area in the Frontal Operculum as a Causal Risk Predictor for Chronic Pain.Pain research & management · 2025Article
- A Review of the Biochemical Diagnostic Biomarkers in Migraine: New Perspectives in Diagnostics.Pain research & management · 2025Review
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Authors and funding
15 authors.
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Abstract
backgroundPrevious studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.
methodsWe utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970-375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.
resultsGenetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.
conclusionThis study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.
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