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Migraine Polygenic Risk Score Associates With Efficacy of Migraine-Specific Drugs

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Migraine Polygenic Risk Score Associates With Efficacy of Migraine-Specific Drugs

Lisette J A Kogelman et al. Neurol Genet.

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.

Figures

Figure 1
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.
Figure 2
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.
Figure 3
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.

Comment in

  • Neurol Genet. 5(6):e368.

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