Migraine polygenic risk score associates with efficacy of migraine-specific drugs
Open Access
- 1 December 2019
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology Genetics
- Vol. 5 (6), e364
- https://doi.org/10.1212/nxg.0000000000000364
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.Keywords
This publication has 32 references indexed in Scilit:
- Common Genetic Variation and Antidepressant Efficacy in Major Depressive Disorder: A Meta-Analysis of Three Genome-Wide Pharmacogenetic StudiesAmerican Journal of Psychiatry, 2013
- pROC: an open-source package for R and S+ to analyze and compare ROC curvesBMC Bioinformatics, 2011
- CYP2D6 Genotype Predicts Antipsychotic Side Effects in Schizophrenia Inpatients: A Retrospective Matched Case-Control StudyNeuropsychobiology, 2009
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- genalex 6: genetic analysis in Excel. Population genetic software for teaching and researchMolecular Ecology Notes, 2005
- The discovery and development of HMG-CoA reductase inhibitorsAtherosclerosis Supplements, 2004
- Genetic and Environmental Influences on Migraine: A Twin Study Across Six CountriesTwin Research, 2003
- Cytochrome P450 polymorphisms and response to antipsychotic therapyPharmacogenomics, 2002
- Advances in pharmacological treatment of migraineExpert Opinion on Investigational Drugs, 2001
- Increased familial risk and evidence of genetic factor in migraineBMJ, 1995