Skip to main content
Top
Published in: The Journal of Headache and Pain 1/2018

Open Access 01-12-2018 | Research article

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

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

Published in: The Journal of Headache and Pain | Issue 1/2018

Login to get access

Abstract

Background

In 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).

Methods

Genotyping 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.

Results

Genotypes 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.

Conclusions

Our 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.
Literature
9.
go back to reference Somerville BW (1972) The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 22(4):355–365CrossRefPubMed Somerville BW (1972) The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 22(4):355–365CrossRefPubMed
18.
go back to reference Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimaki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schurks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Farkkila M, Artto V, Kaunisto M, Vepsalainen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Magi R, Parn K, Hamalainen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkila K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Mannikko M, Mihailov E, Milani L, Gobel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, International Headache Genetics C, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Jarvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, Palotie A (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 48 (8):856–866. doi:https://doi.org/10.1038/ng.3598 Gormley P, Anttila V, Winsvold BS, Palta P, Esko T, Pers TH, Farh KH, Cuenca-Leon E, Muona M, Furlotte NA, Kurth T, Ingason A, McMahon G, Ligthart L, Terwindt GM, Kallela M, Freilinger TM, Ran C, Gordon SG, Stam AH, Steinberg S, Borck G, Koiranen M, Quaye L, Adams HH, Lehtimaki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schurks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Farkkila M, Artto V, Kaunisto M, Vepsalainen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Magi R, Parn K, Hamalainen E, Huang H, Byrnes AE, Franke L, Huang J, Stergiakouli E, Lee PH, Sandor C, Webber C, Cader Z, Muller-Myhsok B, Schreiber S, Meitinger T, Eriksson JG, Salomaa V, Heikkila K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Mannikko M, Mihailov E, Milani L, Gobel H, Esserlind AL, Christensen AF, Hansen TF, Werge T, International Headache Genetics C, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Jarvelin MR, Metspalu A, Kubisch C, Strachan DP, Ferrari MD, Belin AC, Dichgans M, Wessman M, van den Maagdenberg AM, Zwart JA, Boomsma DI, Smith GD, Stefansson K, Eriksson N, Daly MJ, Neale BM, Olesen J, Chasman DI, Nyholt DR, Palotie A (2016) Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 48 (8):856–866. doi:https://​doi.​org/​10.​1038/​ng.​3598
20.
go back to reference Anttila V, Stefansson H, Kallela M, Todt U, Terwindt GM, Calafato MS, Nyholt DR, Dimas AS, Freilinger T, Muller-Myhsok B, Artto V, Inouye M, Alakurtti K, Kaunisto MA, Hamalainen E, de Vries B, Stam AH, Weller CM, Heinze A, Heinze-Kuhn K, Goebel I, Borck G, Gobel H, Steinberg S, Wolf C, Bjornsson A, Gudmundsson G, Kirchmann M, Hauge A, Werge T, Schoenen J, Eriksson JG, Hagen K, Stovner L, Wichmann HE, Meitinger T, Alexander M, Moebus S, Schreiber S, Aulchenko YS, Breteler MM, Uitterlinden AG, Hofman A, van Duijn CM, Tikka-Kleemola P, Vepsalainen S, Lucae S, Tozzi F, Muglia P, Barrett J, Kaprio J, Farkkila M, Peltonen L, Stefansson K, Zwart JA, Ferrari MD, Olesen J, Daly M, Wessman M, van den Maagdenberg AM, Dichgans M, Kubisch C, Dermitzakis ET, Frants RR, Palotie A, International Headache Genetics C (2010) Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet 42(10):869–873. https://doi.org/10.1038/ng.652 CrossRefPubMedPubMedCentral Anttila V, Stefansson H, Kallela M, Todt U, Terwindt GM, Calafato MS, Nyholt DR, Dimas AS, Freilinger T, Muller-Myhsok B, Artto V, Inouye M, Alakurtti K, Kaunisto MA, Hamalainen E, de Vries B, Stam AH, Weller CM, Heinze A, Heinze-Kuhn K, Goebel I, Borck G, Gobel H, Steinberg S, Wolf C, Bjornsson A, Gudmundsson G, Kirchmann M, Hauge A, Werge T, Schoenen J, Eriksson JG, Hagen K, Stovner L, Wichmann HE, Meitinger T, Alexander M, Moebus S, Schreiber S, Aulchenko YS, Breteler MM, Uitterlinden AG, Hofman A, van Duijn CM, Tikka-Kleemola P, Vepsalainen S, Lucae S, Tozzi F, Muglia P, Barrett J, Kaprio J, Farkkila M, Peltonen L, Stefansson K, Zwart JA, Ferrari MD, Olesen J, Daly M, Wessman M, van den Maagdenberg AM, Dichgans M, Kubisch C, Dermitzakis ET, Frants RR, Palotie A, International Headache Genetics C (2010) Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet 42(10):869–873. https://​doi.​org/​10.​1038/​ng.​652 CrossRefPubMedPubMedCentral
21.
go back to reference Chasman DI, Schurks M, Anttila V, de Vries B, Schminke U, Launer LJ, Terwindt GM, van den Maagdenberg AM, Fendrich K, Volzke H, Ernst F, Griffiths LR, Buring JE, Kallela M, Freilinger T, Kubisch C, Ridker PM, Palotie A, Ferrari MD, Hoffmann W, Zee RY, Kurth T (2011) Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet 43(7):695–698. https://doi.org/10.1038/ng.856 CrossRefPubMedPubMedCentral Chasman DI, Schurks M, Anttila V, de Vries B, Schminke U, Launer LJ, Terwindt GM, van den Maagdenberg AM, Fendrich K, Volzke H, Ernst F, Griffiths LR, Buring JE, Kallela M, Freilinger T, Kubisch C, Ridker PM, Palotie A, Ferrari MD, Hoffmann W, Zee RY, Kurth T (2011) Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet 43(7):695–698. https://​doi.​org/​10.​1038/​ng.​856 CrossRefPubMedPubMedCentral
22.
go back to reference Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt GM, Pozo-Rosich P, Winsvold B, Nyholt DR, van Oosterhout WP, Artto V, Todt U, Hamalainen E, Fernandez-Morales J, Louter MA, Kaunisto MA, Schoenen J, Raitakari O, Lehtimaki T, Vila-Pueyo M, Gobel H, Wichmann E, Sintas C, Uitterlinden AG, Hofman A, Rivadeneira F, Heinze A, Tronvik E, van Duijn CM, Kaprio J, Cormand B, Wessman M, Frants RR, Meitinger T, Muller-Myhsok B, Zwart JA, Farkkila M, Macaya A, Ferrari MD, Kubisch C, Palotie A, Dichgans M, van den Maagdenberg AM, International Headache Genetics C (2012) Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet 44 (7):777–782. doi:https://doi.org/10.1038/ng.2307 Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt GM, Pozo-Rosich P, Winsvold B, Nyholt DR, van Oosterhout WP, Artto V, Todt U, Hamalainen E, Fernandez-Morales J, Louter MA, Kaunisto MA, Schoenen J, Raitakari O, Lehtimaki T, Vila-Pueyo M, Gobel H, Wichmann E, Sintas C, Uitterlinden AG, Hofman A, Rivadeneira F, Heinze A, Tronvik E, van Duijn CM, Kaprio J, Cormand B, Wessman M, Frants RR, Meitinger T, Muller-Myhsok B, Zwart JA, Farkkila M, Macaya A, Ferrari MD, Kubisch C, Palotie A, Dichgans M, van den Maagdenberg AM, International Headache Genetics C (2012) Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet 44 (7):777–782. doi:https://​doi.​org/​10.​1038/​ng.​2307
24.
go back to reference Chen H, Chedotal A, He Z, Goodman CS, Tessier-Lavigne M (1997) Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19(3):547–559CrossRefPubMed Chen H, Chedotal A, He Z, Goodman CS, Tessier-Lavigne M (1997) Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19(3):547–559CrossRefPubMed
25.
go back to reference Fujisawa H, Kitsukawa T (1998) Receptors for collapsin/semaphorins. Curr Opin Neurobiol 8(5):587–592CrossRefPubMed Fujisawa H, Kitsukawa T (1998) Receptors for collapsin/semaphorins. Curr Opin Neurobiol 8(5):587–592CrossRefPubMed
28.
go back to reference Punyadeera C, Thijssen VL, Tchaikovski S, Kamps R, Delvoux B, Dunselman GA, de Goeij AF, Griffioen AW, Groothuis PG (2006) Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium. Mol Hum Reprod 12(6):367–375. https://doi.org/10.1093/molehr/gal027 CrossRefPubMed Punyadeera C, Thijssen VL, Tchaikovski S, Kamps R, Delvoux B, Dunselman GA, de Goeij AF, Griffioen AW, Groothuis PG (2006) Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium. Mol Hum Reprod 12(6):367–375. https://​doi.​org/​10.​1093/​molehr/​gal027 CrossRefPubMed
Metadata
Title
The NRP1 migraine risk variant shows evidence of association with menstrual migraine
Authors
Charmaine E. Pollock
Heidi G. Sutherland
Bridget H. Maher
Rodney A. Lea
Larisa M. Haupt
Alison Frith
E. Anne MacGregor
Lyn R. Griffiths
Publication date
01-12-2018
Publisher
Springer Milan
Published in
The Journal of Headache and Pain / Issue 1/2018
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI
https://doi.org/10.1186/s10194-018-0857-z

Other articles of this Issue 1/2018

The Journal of Headache and Pain 1/2018 Go to the issue