Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families

Paavo Häppölä*, Padhraig Gormley, Marjo E. Nuottamo, Ville Artto, Marja Liisa Sumelahti, Markku Nissilä, Petra Keski-Säntti, Matti Ilmavirta, Mari A. Kaunisto, Eija I. Hämäläinen, Samuli Ripatti, Matti Pirinen, Maija Wessman, Aarno Palotie, Mikko Kallela, International Headache Genetics Consortium (IHGC), Thomas Folkmann Hansen (Member of author collaboration), Jes Olesen (Member of author collaboration)

*Corresponding author for this work

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Abstract

Background: Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. Methods: We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. Results: Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02–0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08–0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14–0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26–0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31–0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. Conclusions: The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.

Original languageEnglish
JournalCephalalgia
Volume42
Issue number4-5
Pages (from-to)345-356
Number of pages12
ISSN0333-1024
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© International Headache Society 2021.

Keywords

  • diagnosis criteria
  • headache
  • Migraine
  • polygenic risk score

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