Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Functional gene networks reveal distinct mechanisms segregating in migraine families

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. PET imaging of meningioma with 18F-FLT: a predictor of tumour progression

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Hyperpolarization through ATP-sensitive potassium channels; relevance to migraine pathology

    Research output: Contribution to journalLetterpeer-review

  4. The first step towards personalized risk prediction for common epilepsies

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A meta-analysis uncovers the first sequence variant conferring risk of Bell's palsy

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Changes in the gene expression profile during spontaneous migraine attacks

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Migraine is the most common neurological disorder worldwide and it has been shown to have complex polygenic origins with a heritability of estimated 40-70%. Both common and rare genetic variants are believed to underlie the pathophysiology of the prevalent types of migraine, migraine with typical aura and migraine without aura. However, only common variants have been identified so far. Here we identify for the first time a gene module with rare mutations through a systems genetics approach integrating RNA sequencing data from brain and vascular tissues likely to be involved in migraine pathology in combination with whole genome sequencing of 117 migraine families. We found a gene module in the visual cortex, based on single nuclei RNA sequencing data, that had increased rare mutations in the migraine families and replicated this in a second independent cohort of 1930 patients. This module was mainly expressed by interneurons, pyramidal CA1, and pyramidal SS cells, and pathway analysis showed association with hormonal signalling (thyrotropin-releasing hormone receptor and oxytocin receptor signalling pathways), Alzheimer's disease pathway, serotonin receptor pathway and general heterotrimeric G-protein signalling pathways. Our results demonstrate that rare functional gene variants are strongly implicated in the pathophysiology of migraine. Furthermore, we anticipate that the results can be used to explain the critical mechanisms behind migraine and potentially improving the treatment regime for migraine patients.

Original languageEnglish
JournalBrain
Volume143
Issue number10
Pages (from-to)2945-2956
Number of pages12
ISSN0006-8950
DOIs
Publication statusPublished - 1 Oct 2020

    Research areas

  • complex trait, gene-gene interaction, genetic network, migraine, transcriptomics

ID: 60923171