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Neurol Genet. 2019 Oct 24;5(6):e364. doi: 10.1212/NXG.0000000000000364. eCollection 2019 Dec.

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

Author information

1
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.

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 ∼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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