The NRP1 migraine risk variant shows evidence of association with menstrual migraine

Charmaine E Pollock,Larisa M Haupt,Bridget H Maher,Lyn R Griffiths,Rodney A Lea,Alison Frith,Heidi G Sutherland,E Anne Macgregor

doi:10.1186/s10194-018-0857-z

Charmaine E Pollock, Larisa M Haupt + Show 6 more

Open Access

https://doi.org/10.1186/s10194-018-0857-z

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Abstract

BackgroundIn 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM).MethodsGenotyping of migraine susceptibility SNPs was conducted using the Agena MassARRAY platform on DNA samples from 235 women diagnosed with menstrual migraine as per International Classification for Headache Disorders II (ICHD-II) criteria and 140 controls. Alternative genotyping methods including restriction fragment length polymorphism, pyrosequencing and Sanger sequencing were used for validation. Statistical analysis was performed using PLINK and SPSS.ResultsGenotypes of 34 SNPs were obtained and investigated for their potential association with menstrual migraine. Of these SNPs, rs2506142 located near the neuropilin 1 gene (NRP1), was found to be significantly associated with menstrual migraine (p = 0.003). Genomic risk scores were calculated for all 34 SNPs as well as a subset of 7 SNPs that were nearing individual significance. Overall, this analysis suggested these SNPs to be weakly predictive of MM, but of no prognostic or diagnostic value.ConclusionsOur results suggest that NRP1 may be important in the etiology of MM. It also suggests some genetic commonality between common migraine subtypes (MA and MO) and MM. The identification of associated SNPs may be the starting point to a better understanding of how genetic factors may contribute to the menstrual migraine sub-type.

Highlights

In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38
As per the International Classification for Headache Disorders 3 (ICHD-3) classification, menstrual migraine (MM) is a subclassification of migraine without aura (MO), as menstruation does not appear to be associated with migraine with aura (MA)
Genotyping and quality control Five of the 46 Single-nucleotide polymorphism (SNP) identified by Gormley et al were excluded from the study due to difficulty in designing primers for genotyping the region of interest

Summary

Introduction

In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. Migraine is a genetic disorder that affects more than 10% of the world’s population and is the third leading cause of disability for 15–49 year old women [1]. There is increasing evidence that the late luteal decline in estrogen is a trigger for migraine [9, 10], but potentially the cause for the increase in pain severity [11]. In population- and clinic-based studies, between 20% and 60% of women with migraine report an association with menstruation [12]. This has led to a sub-classification of menstrual migraine (MM), classified in the ICHD-3 appendix for research purposes [2]. Women suffering MM have reported symptoms to be more severe, prolonged and resistant to treatment than conventional migraine [13], and is detrimental to quality of life

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