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

Kogelman, L. J. A., Esserlind, A.-L., Christensen, A. F., Awasthi, S., Ripke, S., Ingason, A., et al. (2019). Migraine polygenic risk score associates with efficacy of migraine-specific drugs. NEUROLOGY-GENETICS, 5(6): e364. doi:10.1212/NXG.0000000000000364.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-F792-F Version Permalink: http://hdl.handle.net/21.11116/0000-0005-F793-E
Genre: Journal Article


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Kogelman, Lisette J. A., Author
Esserlind, Ann-Louise, Author
Christensen, Anne Francke, Author
Awasthi, Swapnil, Author
Ripke, Stephan1, Author              
Ingason, Andres, Author
Davidsson, Olafur B., Author
Erikstrup, Christian, Author
Hjalgrim, Henrik, Author
Ullum, Henrik, Author
Olesen, Jes, Author
Hansen, Thomas Folkmann, Author
Gudbjartsson, Daniel, Author
Gastafsson, Omar, Author
Stefansson, Kari, Author
Stefansson, Hreinn, Author
Porsteinsdottir, Unnur, Author
Andersen, Steffen, Author
Banasik, Karina, Author
Brunak, Soren, Author
Buil, Alfonso, AuthorBurgdorf, Kristoffer, AuthorGregor, Jemec, AuthorJennum, Poul, AuthorNielsen, Kasper Rene, AuthorNyegaard, Mette, AuthorPaarup, Helene Mariana, AuthorPedersen, Ole Birger, AuthorSorensen, Erik, AuthorWerge, Thomas, AuthorAnttila, Verneri, AuthorArtto, Ville, AuthorBelin, Andrea Carmine, Authorde Boer, Irene, AuthorBoomsma I, Dorret, AuthorBorte, Sigrid, AuthorChasman I, Daniel, AuthorCherkas, Lynn, AuthorCormand, Bru, AuthorCuenca-Leon, Ester, AuthorDavey-Smith, George, AuthorDichgans, Martin, Authorvan Duijn, Cornelia, AuthorEsko, Tonu, AuthorFerrari, Michel, AuthorFrants, Rune R., AuthorFreilinger, Tobias, AuthorFurlotte, Nick, AuthorGormley, Padhraig, AuthorGriffiths, Lyn, AuthorHamalainen, Eija, AuthorHiekkala, Marjo, AuthorIkram, M. Arfan, AuthorJarvelin, Marjo-Riitta, AuthorKajanne, Risto, AuthorKallela, Mikko, AuthorKaprio, Jaakko, AuthorKaunisto, Mari, AuthorKubisch, Christian, AuthorKurki, Mitja, AuthorKurth, Tobias, AuthorLauner, Lenore, AuthorLehtimaki, Terho, AuthorLessel, Davor, AuthorLigthart, Lannie, AuthorLitterman, Nadia, Authorvan den Maagdenberg, Arn, AuthorMacaya, Alfons, AuthorMalik, Rainer2, Author              Mangino, Massimo, AuthorMcMahon, George, AuthorMuller-Myhsok, Bertram, AuthorNeale, Benjamin M., AuthorNorthover, Carrie, AuthorNyholt, Dale R., AuthorPalotie, Aarno, AuthorPalta, Priit, AuthorPedersen, Linda, AuthorPedersen, Nancy, AuthorPosthuma, Danielle, AuthorPozo-Rosich, Patricia, AuthorPressman, Alice, AuthorRaitakari, Olli, AuthorSchurks, Markus, AuthorSintas, Celia, AuthorSteinberg, Stacy, AuthorStrachan, David, AuthorTerwindt, Gisela, AuthorVila-Pueyo, Marta, AuthorWessman, Maija, AuthorWinsvold, Bendik S., AuthorZhao, Huiying, AuthorZwart, John-Anker, Author more..
1AG Müller-Myhsok, Bertram, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607154              
2Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565145              


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 Abstract: 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 similar to 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.


 Dates: 2019-10-24
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
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Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 5 (6) Sequence Number: e364 Start / End Page: - Identifier: ISSN: 2376-7839