A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

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




TekijätKogelman LJA, Esserlind AL, Christensen AF, Awasthi S, Ripke S, Ingason A, Davidsson OB, Erikstrup C, Hjalgrim H, Ullum H, Olesen J, Hansen TF, Gudbjartsson D, Gastafsson O, Stefansson K, Stefansson H, Porsteinsdottir U, Andersen S, Banasik K, Brunak S, Buil A, Burgdorf K, Gregor J, Jennum P, Nielsen KR, Nyegaard M, Paarup HM, Pedersen OB, Sorensen E, Werge T, Anttila V, Artto V, Belin AC, de Boer I, Boomsma DI, Borte S, Chasman DI, Cherkas L, Cormand B, Cuenca-Leon E, Davey-Smith G, Dichgans M, van Duijn C, Esko T, Ferrari M, Frants RR, Freilinger T, Furlotte N, Gormley P, Griffiths L, Hamalainen E, Hiekkala M, Ikram MA, Jarvelin MR, Kajanne R, Kallela M, Kaprio J, Kaunisto M, Kubisch C, Kurki M, Kurth T, Launer L, Lehtimaki T, Lessel D, Ligthart L, Litterman N, van den Maagdenberg A, Macaya A, Malik R, Mangino M, McMahon G, Muller-Myhsok B, Neale BM, Northover C, Nyholt DR, Palotie A, Palta P, Pedersen L, Pedersen N, Posthuma D, Pozo-Rosich P, Pressman A, Raitakari O, Schurks M, Sintas C, Steinberg S, Strachan D, Terwindt G, Vila-Pueyo M, Wessman M, Winsvold BS, Zhao HY, Zwart JA, Zwart JA, Zhao HY, Winsvold BS

KustantajaLIPPINCOTT WILLIAMS & WILKINS

Julkaisuvuosi2019

JournalNeurology-Genetics

Tietokannassa oleva lehden nimiNEUROLOGY-GENETICS

Lehden akronyymiNEUROL-GENET

Artikkelin numeroARTN e364

Vuosikerta5

Numero6

Sivujen määrä11

ISSN2376-7839

eISSN2376-7839

DOIhttps://doi.org/10.1212/NXG.0000000000000364

Verkko-osoitehttps://ng.neurology.org/content/5/6/e364

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/45969651


Tiivistelmä
ObjectiveTo assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.MethodsWe 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.ResultsA 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.ConclusionsThe 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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