Dataset Information

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.

SUBMITTER: Happola P

PROVIDER: S-EPMC8988286 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Häppölä Paavo P Gormley Padhraig P Nuottamo Marjo E ME Artto Ville V Sumelahti Marja-Liisa ML Nissilä Markku M Keski-Säntti Petra P Ilmavirta Matti M Kaunisto Mari A MA Hämäläinen Eija I EI Ripatti Samuli S Pirinen Matti M Wessman Maija M Palotie Aarno A Kallela Mikko M

Cephalalgia : an international journal of headache 20211014 4-5

<h4>Background</h4>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.<h4>Methods</h4>We used linear mixed models to study the correlation of ICHD-3 diagnostic criteri ...[more]

PMID: 34648375

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Project description:Background Migraine is a primary headache disorder marked by episodes of moderate to severe headache that is unilateral, throbbing in character, having a duration of 4 h to three days, and associated with nausea, vomiting, photophobia, and phonophobia. Aims Our study aims to determine the frequency of migraine in Pakistan, its association with sociodemographic variables and triggering factors, and the coping mechanisms used. Methods A cross-sectional study was conducted through an online survey from March 19, 2022, to June 15, 2022. The snowball sampling technique was used for data collection. The questions asked included those on sociodemographic information, screening questions, and questions on triggering factors and coping mechanisms. The screening was done using the ICHD-3 criteria and percentages were calculated using SPSS. Results Of the 986 respondents, 393 suffered from migraine. The majority of them were female (78.1%), belonged to the age group 20–29 years (69.2%), and were students (76.1%). 32.8% of the migraineurs had a family history of migraine. Most frequent triggers included sleep disturbance (70.5%), stress (66.7%) and fatigue (64.4%). Of the female migraineurs, 31.8% had menstruation as a trigger. The coping mechanisms used included taking rest, medication, staying in a quiet and dark place, and doing massage. Conclusion The findings suggest that young adults, especially females, with a stressful and sleep-deprived lifestyle are more vulnerable to migraine. However, further studies must focus on trigger synergy and interrelation of triggers that precipitate migraine so a better understanding can be developed for the prevention, diagnosis, and treatment of migraine. Highlights • Females, majorly students, of the age group 20–29 years were the most affected by migraine.• The migraine attacks were mostly triggered by sleep disturbance, stress, excess screen time, loud noise, and missed meals.• The most frequently used coping mechanism by the migraineurs to relieve pain was taking rest.

Project description:ImportanceSpontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome that predominantly affects women. Evidence to date suggests a complex genetic architecture, while a family history is reported for a minority of cases.ObjectiveTo determine the contribution of rare and common genetic variants to SCAD risk in familial cases, the latter via the comparison of a polygenic risk score (PRS) with those with sporadic SCAD and healthy controls.Design, setting, and participantsThis genetic association study analyzed families with SCAD, individuals with sporadic SCAD, and healthy controls. Genotyping was undertaken for all participants. Participants were recruited between 2017 and 2021. A PRS for SCAD was calculated for all participants. The presence of rare variants in genes associated with connective tissue disorders (CTD) was also assessed. Individuals with SCAD were recruited via social media or from a single medical center. A previously published control database of older healthy individuals was used. Data were analyzed from January 2022 to October 2023.ExposuresPRS for SCAD comprised of 7 single-nucleotide variants.Main outcomes and measuresDisease status (familial SCAD, sporadic SCAD, or healthy control) associated with PRS.ResultsA total of 13 families with SCAD (27 affected and 12 unaffected individuals), 173 individuals with sporadic SCAD, and 1127 healthy controls were included. A total of 188 individuals with SCAD (94.0%) were female, including 25 of 27 with familial SCAD and 163 of 173 with sporadic SCAD; of 12 unaffected individuals from families with SCAD, 6 (50%) were female; and of 1127 healthy controls, 672 (59.6%) were female. Compared with healthy controls, the odds of being an affected family member or having sporadic SCAD was significantly associated with a SCAD PRS (where the odds ratio [OR] represents an increase in odds per 1-SD increase in PRS) (affected family member: OR, 2.14; 95% CI, 1.78-2.50; adjusted P = 1.96 × 10-4; sporadic SCAD: OR, 1.63; 95% CI, 1.37-1.89; adjusted P = 5.69 × 10-4). This association was not seen for unaffected family members (OR, 1.03; 95% CI, 0.46-1.61; adjusted P = .91) compared with controls. Further, those with familial SCAD were overrepresented in the top quintile of the control PRS distribution (OR, 3.70; 95% CI, 2.93-4.47; adjusted P = .001); those with sporadic SCAD showed a similar pattern (OR, 2.51; 95% CI, 1.98-3.04; adjusted P = .001). Affected individuals within a family did not share any rare deleterious variants in CTD-associated genes.Conclusions and relevanceExtreme aggregation of common genetic risk appears to play a significant role in familial clustering of SCAD as well as in sporadic case predisposition, although further study is required.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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