University of Oulu

Lisette J.A. Kogelman, Ann-Louise Esserlind, Anne Francke Christensen, Swapnil Awasthi, Stephan Ripke, Andres Ingason, Olafur B. Davidsson, Christian Erikstrup, Henrik Hjalgrim, Henrik Ullum, Jes Olesen, Thomas Folkmann Hansen, DBDS Genomic Consortium, The International Headache Genetics Consortium Neurol Genet Dec 2019, 5 (6) e364; DOI: 10.1212/NXG.0000000000000364

Migraine polygenic risk score associates with efficacy of migraine-specific drugs

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Version: published version
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Language: English
Published: Wolters Kluwer, 2019
Publish Date: 2020-04-15


Objective: To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.

Methods: We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome.

Results: A twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response.

Conclusions: The migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.

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Series: Neurology. Genetics
ISSN: 2376-7839
ISSN-E: 2376-7839
ISSN-L: 2376-7839
Volume: 5
Issue: 6
Article number: e364
DOI: 10.1212/NXG.0000000000000364
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
3112 Neurosciences
3124 Neurology and psychiatry
Funding: This project was financed by a grant from Candys Foundation “CEHEAD” (Prof. Jes Olesen).
Copyright information: © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloadingand sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.