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December 2019; 5 (6) ArticleOpen Access

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

View ORCID ProfileLisette J.A. Kogelman, View ORCID ProfileAnn-Louise Esserlind, Anne Francke Christensen, View ORCID ProfileSwapnil Awasthi, View ORCID ProfileStephan Ripke, Andres Ingason, Olafur B. Davidsson, View ORCID ProfileChristian Erikstrup, View ORCID ProfileHenrik Hjalgrim, View ORCID ProfileHenrik Ullum, View ORCID ProfileJes Olesen, View ORCID ProfileThomas Folkmann Hansen, DBDS Genomic Consortium, The International Headache Genetics Consortium
First published October 24, 2019, DOI: https://doi.org/10.1212/NXG.0000000000000364
Lisette J.A. Kogelman
From the 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.
PhD
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  • ORCID record for Lisette J.A. Kogelman
Ann-Louise Esserlind
From the 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.
MD, PhD
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  • ORCID record for Ann-Louise Esserlind
Anne Francke Christensen
From the 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.
MD, PhD
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Swapnil Awasthi
From the 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.
MSc
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  • ORCID record for Swapnil Awasthi
Stephan Ripke
From the 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.
PhD
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  • ORCID record for Stephan Ripke
Andres Ingason
From the 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.
PhD
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Olafur B. Davidsson
From the 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.
MSc
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Christian Erikstrup
From the 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.
PhD
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  • ORCID record for Christian Erikstrup
Henrik Hjalgrim
From the 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.
PhD, DMSc
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  • ORCID record for Henrik Hjalgrim
Henrik Ullum
From the 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.
PhD
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Jes Olesen
From the 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.
DMSc
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Thomas Folkmann Hansen
From the 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.
PhD
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  • ORCID record for Thomas Folkmann Hansen
From the 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.
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Migraine polygenic risk score associates with efficacy of migraine-specific drugs
Lisette J.A. Kogelman, Ann-Louise Esserlind, Anne Francke Christensen, Swapnil Awasthi, Stephan Ripke, Andres Ingason, Olafur B. Davidsson, Christian Erikstrup, Henrik Hjalgrim, Henrik Ullum, Jes Olesen, Thomas Folkmann Hansen, DBDS Genomic Consortium, The International Headache Genetics Consortium
Neurol Genet Dec 2019, 5 (6) e364; DOI: 10.1212/NXG.0000000000000364

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    Figure 1 Association of the polygenic risk score with acute treatment response

    ORs and the 95% CI are shown on the left-hand side, and the corresponding forest plot is shown on the right-hand side. An OR below 1 represents a lower response rate to the drug. An OR above 1 represents a higher response rate to the drug. Migraine-specific acute treatment includes both triptan and ergotamine, as both are acting on the same 5-HT1B/D receptors. Migraine nonspecific treatment is represented by the weak analgesics. CI = confidence interval; OR = odds ratio.

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    Figure 2 Associations of the polygenic risk score with prophylactic treatment response

    ORs and the 95% CI are shown on the left-hand side, and the corresponding forest plot is shown on the right-hand side. An OR below 1 represents a lower response rate to the drug. An OR above 1 represents a higher response rate to the drug. Acute treatment includes both triptan and ergotamine, as both are acting on the same 5-HT1B/D receptors. Prophylactic treatment response includes all questioned treatments summed up (positive response to any prophylactic drug vs response to none). ACE = angiotensin-converting enzyme; CI = confidence interval; OR = odds ratio.

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    Figure 3 Replication of the association of the polygenic risk score (PRS) with acute treatment response

    Odds ratio by PRS within each 20 percentiles for n = 5,616 triptan users in the Danish Blood Donor Study replication cohort.

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