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Family-Based Association Study of Chromosome 6p12.2-p21.1 Migraine Locus

Authors

  • Agustín Oterino MD,

    Corresponding author
    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Maria Toriello Biologist,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Jesus Castillo MD,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Vicente González-Quitanilla MD,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Pablo Sánchez-Velasco MD,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Ana Alonso Tech,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Nuria Ruiz-Lavilla MD,

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Julio Pascual MD

    1. From the University Hospital Marques de Valdecilla – Neurology, Santander, Cantabria, Spain (A. Oterino, M. Toriello, V. González-Quitanilla, and A. Alonso); Servicio Canatabro de Salud – Health Center of Camargo, Camargo, Spain (J. Castillo); University Hospital Marques de Valdecilla – Immunology, Santander, Cantabria, Spain (P. Sánchez-Velasco); University Hospital La Candelaria – Neurology, Santa Cruz de Tenerife, Tenerife, Spain (N. Ruiz-Lavilla); University Hospital – Clinical Neuroscience, Oviedo, Spain (J. Pascual).
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  • Conflict of Interest: None.

A. Oterino, University Hospital Marques de Valdecilla – Neurology, avda Valdecilla sn, Santander, 39011 Cantabria, Spain, email: agustin.oterino@telefonica.net

Abstract

Background.— One of the genome-wide linkage studies performed in migraine has yielded a significant linkage of migraine (with and without aura) with markers located at 6p12.2-21.1. This locus (named MIGR3) has not been replicated in the only genome-wide association scan study performed to date or in previous genome-wide linkage studies.

Objective.— Our objective had been to replicate the MIGR3 locus performing a family-based association study.

Methods.— A sample of 594 subjects belonging to 134 migraine families of diverse complexity underwent genotyping for the markers previously published as linked at 6p12.2-21.1 migraine locus. Family-based association test, under different models of inheritance, and also the model-free TDT analysis were performed.

Results.— The best result was obtained with the D6S1650 marker under the additive model (rank [S observed] = 265.0; permuted P = .0006), using family-based association test program (HBAT subprogram). Similar results were obtained with the model-free TDTPHASE algorithm (P < .0001, corrected). Nominal significant P values were obtained for D6S1630, D6S452, and D6S257. After correction for multiple testing with the stratified false-discovery rate, all markers showed significant association (P < .0001).

Conclusion.— We corroborated that the MIGR3 locus at 6p12 is a genetic risk for migraine with and without aura.

(Headache 2012;52:393-399)

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