Open AccessPolygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families
Author(s) -
Paavo Häppölä,
Padhraig Gormley,
Marjo Eveliiuottamo,
Ville Artto,
MarjaLiisa Sumelahti,
M Nissilä,
Petra Keski-Säntti,
Matti Ilmavirta,
Mari A. Kaunisto,
Eija Hämäläinen,
Samuli Ripatti,
Matti Pirinen,
Maija Wessman,
Aarno Palotie,
Mikko Kallela
Publication year - 2021
Publication title -
cephalalgia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.57
H-Index - 125
eISSN - 1468-2982
pISSN - 0333-1024
DOI - 10.1177/03331024211045651
Subject(s) - migraine , medicine , international classification of headache disorders , migraine with aura , aura , cohort , chronic migraine , physical therapy , pediatrics
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.