Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cephalalgia |
| Vol/bind | 42 |
| Udgave nummer | 4-5 |
| Sider (fra-til) | 345-356 |
| Antal sider | 12 |
| ISSN | 0333-1024 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PG is a current employee and/or stockholder of GlaxoSmithKline but the work was conducted while employed by Massachusetts General Hospital, Boston, MA, USA. AP is a member of AstraZeneca Genomics Advisory Board and is the Scientific Director of the public-private partnership project FinnGen, which has 12 industry partners that provide funding for the FinnGen project. MK has served on Advisory Boards for MSD, Allergan, TEVA, Lilly and Lundbeck, has received funding for travel and/or speaker honoraria from MSD, Allergan, TEVA, Novartis, and Genzyme; has received compensation for producing educational material from TEVA and Allergan; has received research support from Helsinki University Central Hospital; and holds stock/stock options and/or has received Board of Directors compensation from Helsinki Headache Center. VA has served on Advisory Boards for Allergan, TEVA, Lilly and Lundbeck, has received funding for travel and/or speaker honoraria from TEVA, Novartis, and Sanofi; and has received compensation for producing educational material from Lilly, TEVA and Novartis. Part of MAK’s salary is covered by the public-private partnership research project FinnGen, funded by 12 international pharmaceutical companies and Business Finland.
Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Wellcome Trust (grant numbers WT089062, 098051 to AP); the Academy of Finland (grant numbers 200923, 251704, 286500 to AP, and 139795 to MW, and 285380 to SR); the Academy of Finland Center of Excellence for Complex Disease Genetics (grant numbers 213506, 129680, 312062); the EuroHead project (LSM-CT-2004-504837); FP7-EUROHEADPAIN-no.602633; ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413); EU/SYNSYS-Synaptic Systems (grant number 242167 to AP); the Sigrid Juselius Foundation, Finland (to AP and MP); the Folkhälsan Research Foundation, Finland (to MW); Medicinska Understödsföreningen Liv & Hälsa (to MW); the Helsinki University Central Hospital (to MK); the Finnish Foundation for Cardiovascular Research (to SR); and University of Helsinki HiLIFE Fellow grant (to SR).
Publisher Copyright:
© International Headache Society 2021.
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