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. 2017 Aug;136(8):999-1008.
doi: 10.1007/s00439-017-1816-5. Epub 2017 Jun 27.

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

Claudia Pisanu  1   2 , Martin Preisig  3 , Enrique Castelao  3 , Jennifer Glaus  4 , Giorgio Pistis  3 , Alessio Squassina  2 , Maria Del Zompo  2 , Kathleen R Merikangas  4 , Gérard Waeber  5 , Peter Vollenweider  5 , Jessica Mwinyi #  6 , Helgi B Schiöth #  1
Affiliations

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

Claudia Pisanu et al. Hum Genet. 2017 Aug.

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.

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Conflict of interest statement

Funding

This study was supported by a grant from the Swedish Society for Medical Research (SSMF) to JM, a grant from the Swedish Research Council to HBS, and in part by the Intramural Research Program of the National Institute of Mental Health (ZIAMH002932). The CoLaus|PsyCoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, the Swiss National Science Foundation (Grants 3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, and 33CS30-148401).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Random forest model including 21 SNPs previously associated with migraine. The first 30 variables with the highest mean decrease accuracy are plotted. Twenty-one migraine-associated SNP were shown to induce a positive change in mean decrease accuracy. These SNPs were thus considered to have a relevant influence on the model and were chosen for inclusion in the GRS. GRS genetic risk score, SNP single-nucleotide polymorphism
Fig. 2
Fig. 2
Box and whisker plot of GRS in subjects with migraine or migraine subtypes compared to controls. Mann–Whitney test showed a significant association between the genetic risk score and migraine (U = 522,400, p = 0.02) or MWOA (U = 329,900, p = 0.003), but not the MWA subtype (U = 189,200, p = 0.8). * <0.05, ** <0.005. GRS genetic risk score, MWA migraine with aura, MWOA migraine without aura
See this image and copyright information in PMC

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