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

Journal

Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 21 03 2019
accepted: 04 09 2019
entrez: 25 12 2019
pubmed: 25 12 2019
medline: 25 12 2019
Statut: epublish

Résumé

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

Identifiants

DOI: 10.1212/NXG.0000000000000364 PMID: 31872049 PMC: PMC6878840
pubmed: 31872049
doi: 10.1212/NXG.0000000000000364
pii: NG2019010579
pmc: PMC6878840
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e364

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Lisette J A Kogelman (LJA)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0001-9782-7810

Ann-Louise Esserlind (AL)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0001-9561-3595

Anne Francke Christensen (A)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.

Swapnil Awasthi (S)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0002-9692-8123

Stephan Ripke (S)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0003-3622-835X

Andres Ingason (A)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.

Olafur B Davidsson (OB)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.

Christian Erikstrup (C)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0001-6551-6647

Henrik Hjalgrim (H)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0002-4436-6798

Henrik Ullum (H)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0001-7306-9058

Jes Olesen (J)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0002-6712-2702

Thomas Folkmann Hansen (T)

Danish Headache Center (L.J.A.K., A.-L.E., A.F.C., O.B.D., J.O., T.F.H.), Department of Neurology, Rigshospitalet Glostrup, Denmark; Department of Psychiatry and Psychotherapy (S.A., S.R.), Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit (S.R.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.R.), Broad Institute of MIT and Harvard, Cambridge, MA; Mental Health Centre Sct Hans (A.I.), Institute of Biological Psychiatry, Roskilde; Department of Clinical Immunology (C.E.), Aarhus University Hospital; Department of Epidemiology Research (H.H.), Statens Serum Institut, Copenhagen; and Department of Clinical Immunology (H.U.), the Blood Bank, Rigshospitalet, Copenhagen University Hospital, Denmark.
ORCID: 0000-0001-6703-7762

Classifications MeSH