Migraine polygenic risk score associates with efficacy of migraine-specific drugs |
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Author: | Kogelman, Lisette J. A.1,2; Esserlind, Ann-Louise1,2,3; Christensen, Anne Francke1,3; |
Organizations: |
1Rigshosp Glostrup, Dept Neurol, Danish Headache Ctr, Glostrup, Denmark. 2Rigshosp Glostrup, Glostrup, Denmark. 3Univ Copenhagen, Rigshosp, Glostrup Hosp, Danish Headache Ctr,Dept Neurol, Copenhagen, Denmark.
4Charite, Dept Psychiat & Psychotherapy, Berlin, Germany.
5Charite, Berlin, Germany. 6Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. 7Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. 8Massachusetts Gen Hosp, Boston, MA 02114 USA. 9Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. 10Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Roskilde, Denmark. 11Mental Hlth Ctr Sct Hans, Roskilde, Denmark. 12deCODE Genet Inc, Reykjavik, Iceland. 13Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark. 14Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. 15Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Blood Bank, Copenhagen, Denmark. 16Copenhagen Univ Hosp, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark. 17Rigshosp, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark. 18deCODE Genet, Reykjavik, Iceland. 19Copenhagen Business Sch, Dept Finance, Copenhagen, Denmark. 20Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Copenhagen, Denmark. 21Sealand Univ Hosp, Dept Clin Med, Roskilde, Denmark. 22Univ Copenhagen, Dept Clin Neurophysiol, Copenhagen, Denmark. 23Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark. 24Aarhus Univ, Dept Biomed, Aarhus, Denmark. 25Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark. 26Naestved Hosp, Dept Clin Immunol, Naestved, Denmark. 27Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark. 28Helsinki Univ Cent Hosp, Dept Neurol, Helsinki, Finland. 29Karolinska Inst, Stockholm, Sweden. 30Leiden Univ, Med Ctr, Leiden, Netherlands. 31Vrije Univ Amsterdam, Amsterdam, Netherlands. 32Oslo Univ Hosp, Oslo, Norway. 33Univ Oslo, Oslo, Norway. 34Harvard Med Sch, Boston, MA 02115 USA. 35Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. 36Univ Barcelona, Barcelona, Spain. 37Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England. 38Inst Stroke & Dementia Res, Munich, Germany. 39Erasmus MC, Rotterdam, Netherlands. 40Univ Tartu, Genome Ctr, Tartu, Estonia. 41Univ Tubingen, Tubingen, Germany. 4223AndMe Inc, Mountain View, CA USA. 43Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia. 44Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. 45Folkhalsan Inst Genet, Helsinki, Finland. 46Jarvelin Univ Oulu, Bioctr, Oulu, Finland. 47Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. 48NIA, Bethesda, MD 20892 USA. 49Unvi 3 Tampere, Sch Med, Tampere, Finland. 50Vall dHebron Res Inst, Barcelona, Spain. 51Max Planck Inst Psychiat, Munich, Germany. 52Univ Autonoma Barcelona, Vall dHebron Res Inst, Headache Res Grp, Barcelona, Spain. 53Vall dHebron Univ Hosp, Neurol Dept, Headache Unit, Barcelona, Spain. 54Sutter Hlth, Sacramento, CA USA. 55Univ Turku, Dept Med, Turku, Finland. 56St Georges Univ London, Populat Hlth Res Inst, Cranmer Terrace, London, England. |
Format: | article |
Version: | published version |
Access: | open |
Online Access: | PDF Full Text (PDF, 0.3 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe2020041516656 |
Language: | English |
Published: |
Wolters Kluwer,
2019
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Publish Date: | 2020-04-15 |
Description: |
AbstractObjective: 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. see all
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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 |
OADOI: | https://oadoi.org/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 |
Subjects: | |
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. |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |