The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

Ann-Louise Esserlind; Anne Francke Christensen; Stacy Steinberg; Niels Grarup; Oluf Pedersen; Torben Hansen; Thomas Werge; Thomas Folkmann Hansen; Lise Lotte N Husemoen; Allan René Linneberg; Esben Budtz-Jørgensen; Maria Lurenda Westergaard; Hreinn Stefansson; Jes Olesen

doi:10.1177/0333102415570492

The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

Ann-Louise Esserlind, Anne Francke Christensen, Stacy Steinberg, Niels Grarup, Oluf Pedersen, Torben Hansen, Thomas Werge, Thomas Folkmann Hansen, Lise Lotte N Husemoen, Allan René Linneberg, Esben Budtz-Jørgensen, Maria Lurenda Westergaard, Hreinn Stefansson, Jes Olesen

19 Citations (Scopus)

Abstract

INTRODUCTION: The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population.

METHODS: Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model.

RESULTS: We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks.

CONCLUSION: Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.

Original language	English
Journal	Cephalalgia : an international journal of headache
Volume	36
Issue number	7
Pages (from-to)	1-9
Number of pages	9
ISSN	0333-1024
DOIs	https://doi.org/10.1177/0333102415570492
Publication status	Published - 1 Jun 2016

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Esserlind, A.-L., Christensen, A. F., Steinberg, S., Grarup, N., Pedersen, O., Hansen, T., Werge, T., Hansen, T. F., Husemoen, L. L. N., Linneberg, A. R., Budtz-Jørgensen, E., Westergaard, M. L., Stefansson, H., & Olesen, J. (2016). The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample. Cephalalgia : an international journal of headache, 36(7), 1-9. https://doi.org/10.1177/0333102415570492

The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample. / Esserlind, Ann-Louise; Christensen, Anne Francke; Steinberg, Stacy et al.
In: Cephalalgia : an international journal of headache, Vol. 36, No. 7, 01.06.2016, p. 1-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Esserlind, A-L, Christensen, AF, Steinberg, S, Grarup, N , Pedersen, O , Hansen, T , Werge, T, Hansen, TF, Husemoen, LLN, Linneberg, AR , Budtz-Jørgensen, E, Westergaard, ML, Stefansson, H & Olesen, J 2016, 'The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample', Cephalalgia : an international journal of headache, vol. 36, no. 7, pp. 1-9. https://doi.org/10.1177/0333102415570492

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abstract = "INTRODUCTION: The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population.METHODS: Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model.RESULTS: We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks.CONCLUSION: Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.",

author = "Ann-Louise Esserlind and Christensen, {Anne Francke} and Stacy Steinberg and Niels Grarup and Oluf Pedersen and Torben Hansen and Thomas Werge and Hansen, {Thomas Folkmann} and Husemoen, {Lise Lotte N} and Linneberg, {Allan Ren{\'e}} and Esben Budtz-J{\o}rgensen and Westergaard, {Maria Lurenda} and Hreinn Stefansson and Jes Olesen",

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T1 - The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

AU - Esserlind, Ann-Louise

AU - Christensen, Anne Francke

AU - Steinberg, Stacy

AU - Grarup, Niels

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Werge, Thomas

AU - Hansen, Thomas Folkmann

AU - Husemoen, Lise Lotte N

AU - Linneberg, Allan René

AU - Budtz-Jørgensen, Esben

AU - Westergaard, Maria Lurenda

AU - Stefansson, Hreinn

AU - Olesen, Jes

PY - 2016/6/1

Y1 - 2016/6/1

N2 - INTRODUCTION: The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population.METHODS: Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model.RESULTS: We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks.CONCLUSION: Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.

AB - INTRODUCTION: The objective of the study was to follow up and to test whether 12 previously identified migraine-associated single nucleotide polymorphisms were associated as risk factors and/or modifying factors for severe migraine traits in a Danish clinic-based population.METHODS: Semi-structured migraine interviews, blood sampling and genotyping were performed on 1806 unrelated migraineurs recruited from the Danish Headache Center. Genotyping was also performed on a control group of 6415 people with no history of migraine. Association analyses were carried out using logistic regression and odds ratios were calculated assuming an additive model for risk. The proxies for severe migraine traits (early onset of migraine; many lifetime attacks, prolonged migraine and tendency to chronification of migraine) were tested against the 12 single nucleotide polymorphisms and a combined genetic score in both a case-control and case-only logistic regression model.RESULTS: We successfully replicated five out of the 12 previously reported loci and confirmed the same direction of effects for all the 12 single nucleotide polymorphisms. In line with the recently published genome-wide association meta-analysis, the associations were significant for all migraine and migraine without aura but not for migraine with typical aura. Two single nucleotide polymorphisms (rs2274316 and rs11172113) conferred risk of many lifetime attacks inthe case-control analysis. In the case-only analysis, only three single nucleotide polymorphisms showed nominal association with many lifetime attacks and prolonged migraine attacks.CONCLUSION: Our study supports previously reported findings on the association of several single nucleotide polymorphisms with migraine. It also suggests that the migraine susceptibility loci may be risk factors for severe migraine traits.

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DO - 10.1177/0333102415570492

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SN - 0333-1024

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SP - 1

EP - 9

JO - Cephalalgia : an international journal of headache

JF - Cephalalgia : an international journal of headache

IS - 7

ER -

The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample

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