RT Journal Article
SR Electronic
T1 Migraine polygenic risk score associates with efficacy of migraine-specific drugs
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e364
DO 10.1212/NXG.0000000000000364
VO 5
IS 6
A1 Kogelman, Lisette J.A.
A1 Esserlind, Ann-Louise
A1 Francke Christensen, Anne
A1 Awasthi, Swapnil
A1 Ripke, Stephan
A1 Ingason, Andres
A1 Davidsson, Olafur B.
A1 Erikstrup, Christian
A1 Hjalgrim, Henrik
A1 Ullum, Henrik
A1 Olesen, Jes
A1 Folkmann Hansen, Thomas
A1 ,
YR 2019
UL http://ng.neurology.org/content/5/6/e364.abstract
AB 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.ACE=angiotensin-converting enzyme; AUC=area under the curve; CI=confidence interval; DBDS=Danish Blood Donor Study; GWAS=genome-wide association study; HET=heterozygosity; IHGC=International Headache Genetics Consortium; LD=linkage disequilibrium; MA=migraine with aura; MO=migraine without aura; OR=odds ratio; PC=principal component; PRS=polygenic risk score; SNP=single nucleotide polymorphism