A genetic risk score is differentially associated with migraine with and without aura

Claudia Pisanu,Enrique Castelao,Giorgio Pistis,Jennifer Glaus,Maria Del Zompo,Jessica Mwinyi,Kathleen R Merikangas,Helgi B Schiöth,Martin Preisig,Gérard Waeber,Peter Vollenweider,Alessio Squassina

doi:10.1007/s00439-017-1816-5

Abstract

Although a number of migraine-associated single-nucleotide polymorphisms (SNP) with small effect size have been identified, little is known about the additive impact of these variants on migraine risk, frequency and severity. We investigated to what extent a genetic risk score (GRS) based on recently published, novel migraine-associated SNPs is associated with migraine prevalence, subtypes and severity in a large population-based sample. The sample comprised 446 subjects with migraine and 2511 controls from the CoLaus/PsyCoLaus study. Fifty-four SNPs earlier associated with migraine were selected. SNPs with a low impact on migraine prevalence in our sample were excluded using random forest. We combined the remaining 21 SNPs into a GRS and analyzed the association with migraine using logistic regression models. The GRS was significantly associated with migraine (OR = 1.56, p = 0.02) and migraine without aura (MWOA) (OR = 2.01, p = 0.003), but not with migraine with aura (MWA). The GRS was not associated with migraine frequency, intensity or interference with daily activities. We show that a GRS combining multiple genetic risk variants is associated with MWOA but not MWA, suggesting a different genetic susceptibility background underlying the two forms of migraine.

Highlights

Migraine is a disabling disorder characterized by recurrent episodes of headache attacks and associated symptoms
We show that a genetic risk score (GRS) combining multiple genetic risk variants is associated with migraine without aura (MWOA) but not migraine with aura (MWA), suggesting a different genetic susceptibility background underlying the two forms of migraine
We demonstrate that the GRS based on single-nucleotide polymorphisms (SNP) previously identified in GWAS studies or meta-analyses to be associated with migraine impacts MWOA, but not the risk for MWA

Summary

Introduction

Migraine is a disabling disorder characterized by recurrent episodes of headache attacks and associated symptoms. With a lifetime prevalence of 18% in women and 6% in men, migraine is an extremely common disorder (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators 2016). Migraine without aura (MWOA) is the most common form of migraine and is characterized by recurrent severe headache attacks lasting 4–72 h with associated gastrointestinal and autonomic symptoms [Headache Classification Committee of the International Headache Society (IHS) 2013; Headache Classification Subcommittee of the International Headache Society 2004]. Up to one-third of affected individuals experience transient focal neurological symptoms before or during the headache attack [(migraine with aura (MWA)] [Headache Classification Committee of the International Headache Society (IHS) 2013; Headache. A number of hypotheses have been advanced, the pathogenesis of migraine is hitherto not fully understood, which is, of urgent need for the development of novel treatment approaches

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