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

IHGC; Paavo Häppölä; Padhraig Gormley; Marjo E. Nuottamo; Ville Artto; Marja-Liisa Sumelahti; Markku Nissila; Petra Keski-Santti; Matti Ilmavirta; Mari A. Kaunisto; Eija Hamalainen; Samuli Ripatti; Matti Pirinen; Maija Wessman; Aarno Palotie; Mikko Kallela

doi:10.1177/03331024211045651

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

IHGC
, Paavo Häppölä^*
, Padhraig Gormley
, Marjo E. Nuottamo
, Ville Artto
, Marja-Liisa Sumelahti
, Markku Nissila
, Petra Keski-Santti
, Matti Ilmavirta
, Mari A. Kaunisto
, Eija Hamalainen
, Samuli Ripatti
, Matti Pirinen
, Maija Wessman
, Aarno Palotie
, Mikko Kallela

^*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

17 Sitaatiot (Scopus)

15 Lataukset (Pure)

Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	03331024211045651
Sivumäärä	12
Julkaisu	Cephalalgia
Vuosikerta	42
Numero	4-5
Varhainen verkossa julkaisun päivämäärä	14 lokak. 2021
DOI - pysyväislinkit	https://doi.org/10.1177/03331024211045651
Tila	Julkaistu - huhtik. 2022
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

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-EUROHEADPAINno.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 Folkhalsan Research Foundation, Finland (to MW); Medicinska Understodsforeningen Liv & Halsa (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).

YK:n kestävän kehityksen tavoitteet

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SDG 3 – Hyvä terveys ja hyvinvointi

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10.1177/03331024211045651Lisenssi: CC BY

03331024211045651Final published version, 371 KBLisenssi: CC BY

https://urn.fi/URN:NBN:fi:tuni-202201311737Lisenssi: CC BY

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IHGC, Häppölä, P., Gormley, P., Nuottamo, M. E., Artto, V., Sumelahti, M.-L., Nissila, M., Keski-Santti, P., Ilmavirta, M., Kaunisto, M. A., Hamalainen, E., Ripatti, S., Pirinen, M., Wessman, M., Palotie, A., & Kallela, M. (2022). Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families. Cephalalgia, 42(4-5), Artikkeli 03331024211045651. https://doi.org/10.1177/03331024211045651

@article{85a036e47cca4291a70d74fc414fa40e,

title = "Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families",

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.",

keywords = "Migraine, headache, diagnosis criteria, polygenic risk score, DISEASE",

author = "IHGC and Paavo H{\"a}pp{\"o}l{\"a} and Padhraig Gormley and Nuottamo, \{Marjo E.\} and Ville Artto and Marja-Liisa Sumelahti and Markku Nissila and Petra Keski-Santti and Matti Ilmavirta and Kaunisto, \{Mari A.\} and Eija Hamalainen and Samuli Ripatti and Matti Pirinen and Maija Wessman and Aarno Palotie and Mikko Kallela",

year = "2022",

month = apr,

doi = "10.1177/03331024211045651",

language = "English",

volume = "42",

journal = "Cephalalgia",

issn = "0333-1024",

publisher = "Sage Publications",

number = "4-5",

}

IHGC, Häppölä, P, Gormley, P, Nuottamo, ME, Artto, V, Sumelahti, M-L, Nissila, M, Keski-Santti, P, Ilmavirta, M, Kaunisto, MA, Hamalainen, E, Ripatti, S, Pirinen, M, Wessman, M, Palotie, A & Kallela, M 2022, 'Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families', Cephalalgia, Vuosikerta 42, Nro 4-5, 03331024211045651. https://doi.org/10.1177/03331024211045651

TY - JOUR

T1 - Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families

AU - IHGC

AU - Häppölä, Paavo

AU - Gormley, Padhraig

AU - Nuottamo, Marjo E.

AU - Artto, Ville

AU - Sumelahti, Marja-Liisa

AU - Nissila, Markku

AU - Keski-Santti, Petra

AU - Ilmavirta, Matti

AU - Kaunisto, Mari A.

AU - Hamalainen, Eija

AU - Ripatti, Samuli

AU - Pirinen, Matti

AU - Wessman, Maija

AU - Palotie, Aarno

AU - Kallela, Mikko

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

KW - Migraine

KW - headache

KW - diagnosis criteria

KW - polygenic risk score

KW - DISEASE

U2 - 10.1177/03331024211045651

DO - 10.1177/03331024211045651

M3 - Article

SN - 0333-1024

VL - 42

JO - Cephalalgia

JF - Cephalalgia

IS - 4-5

M1 - 03331024211045651

ER -

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

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

Pääsy asiakirjaan

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