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

Familial analysis reveals rare risk variants for migraine in regulatory regions

Research output: Contribution to journalJournal articleResearchpeer-review

  1. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Letter to the editor regarding "Have you ever experienced a headache of any kind?"

    Research output: Contribution to journalLetterResearchpeer-review

  3. No central action of CGRP antagonising drugs in the GTN mouse model of migraine

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The impact of low-risk genetic variants in self-limited epilepsy with centrotemporal spikes aka Rolandic epilepsy

    Research output: Contribution to journalComment/debateResearchpeer-review

View graph of relations

The most recent genome-wide association study of migraine increased the total number of known migraine risk loci to 38. Still, most of the heritability of migraine remains unexplained, and it has been suggested that rare gene dysregulatory variants play an important role in migraine etiology. Addressing the missing heritability of migraine, we aim to fine-map signals from the known migraine risk loci to regulatory mechanisms and associate these to downstream genic targets. We analyzed a large cohort of whole-genome sequenced patients from extended migraine pedigrees (1040 individuals from 155 families). We test for association between rare variants segregating in regulatory regions with migraine. The findings were replicated in an independent case-control cohort (2027 migraineurs, 1650 controls). We report an increased burden of rare variants in one CpG island and three polycomb group response elements near four migraine risk loci. We found that the association is independent of the common risk variants in the loci. The regulatory regions are suggested to affect different genes than those originally tagged by the index SNPs of the migraine loci. Families with familial clustering of migraine have an increased burden of rare variants in regulatory regions near known migraine risk loci, with effects that are independent of the variants in the loci. The possible regulatory targets suggest different genes than those originally tagged by the index SNPs of the migraine loci.

Original languageEnglish
JournalNeurogenetics
ISSN1364-6745
DOIs
Publication statusPublished - 19 Feb 2020

    Research areas

  • Family study, Gene regulation, Genetics, Genome-wide, Migraine, Rare-variant association analysis

ID: 59483068