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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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Kogelman, Lisette J. A., Autor
Esserlind, Ann-Louise, Autor
Christensen, Anne Francke, Autor
Awasthi, Swapnil, Autor
Ripke, Stephan, Autor
Ingason, Andres, Autor
Davidsson, Olafur B., Autor
Erikstrup, Christian, Autor
Hjalgrim, Henrik, Autor
Ullum, Henrik, Autor
Olesen, Jes, Autor
Hansen, Thomas Folkmann, Autor
Gudbjartsson, Daniel, Autor
Gastafsson, Omar, Autor
Stefansson, Kari, Autor
Stefansson, Hreinn, Autor
Porsteinsdottir, Unnur, Autor
Andersen, Steffen, Autor
Banasik, Karina, Autor
Brunak, Soren, Autor
Buil, Alfonso, AutorBurgdorf, Kristoffer, AutorGregor, Jemec, AutorJennum, Poul, AutorNielsen, Kasper Rene, AutorNyegaard, Mette, AutorPaarup, Helene Mariana, AutorPedersen, Ole Birger, AutorSorensen, Erik, AutorWerge, Thomas, AutorAnttila, Verneri, AutorArtto, Ville, AutorBelin, Andrea Carmine, Autorde Boer, Irene, AutorBoomsma I, Dorret, AutorBorte, Sigrid, AutorChasman I, Daniel, AutorCherkas, Lynn, AutorCormand, Bru, AutorCuenca-Leon, Ester, AutorDavey-Smith, George, AutorDichgans, Martin, Autorvan Duijn, Cornelia, AutorEsko, Tonu, AutorFerrari, Michel, AutorFrants, Rune R., AutorFreilinger, Tobias, AutorFurlotte, Nick, AutorGormley, Padhraig, AutorGriffiths, Lyn, AutorHamalainen, Eija, AutorHiekkala, Marjo, AutorIkram, M. Arfan, AutorJarvelin, Marjo-Riitta, AutorKajanne, Risto, AutorKallela, Mikko, AutorKaprio, Jaakko, AutorKaunisto, Mari, AutorKubisch, Christian, AutorKurki, Mitja, AutorKurth, Tobias, AutorLauner, Lenore, AutorLehtimaki, Terho, AutorLessel, Davor, AutorLigthart, Lannie, AutorLitterman, Nadia, Autorvan den Maagdenberg, Arn, AutorMacaya, Alfons, AutorMalik, Rainer, AutorMangino, Massimo, AutorMcMahon, George, AutorMuller-Myhsok, Bertram1, Autor           Neale, Benjamin M., AutorNorthover, Carrie, AutorNyholt, Dale R., AutorPalotie, Aarno, AutorPalta, Priit, AutorPedersen, Linda, AutorPedersen, Nancy, AutorPosthuma, Danielle, AutorPozo-Rosich, Patricia, AutorPressman, Alice, AutorRaitakari, Olli, AutorSchurks, Markus, AutorSintas, Celia, AutorSteinberg, Stacy, AutorStrachan, David, AutorTerwindt, Gisela, AutorVila-Pueyo, Marta, AutorWessman, Maija, AutorWinsvold, Bendik S., AutorZhao, Huiying, AutorZwart, John-Anker, Autor mehr..
Affiliations:
1RG Statistical Genetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2040288              

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 Zusammenfassung: 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.

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 Datum: 2019
 Publikationsstatus: Online veröffentlicht
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 Art der Begutachtung: -
 Identifikatoren: ISI: 000512893600002
DOI: 10.1212/NXG.0000000000000364
 Art des Abschluß: -

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Titel: NEUROLOGY-GENETICS
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 5 (6) Artikelnummer: e364 Start- / Endseite: - Identifikator: ISSN: 2376-7839