A high-density association screen of 155 ion transport genes for involvement with common migraine

Dale R. Nyholt, K. Steven LaForge, Mikko Kallela, Kirsi Alakurtti, Verneri Anttila, Markus Färkkilä, Eija Hämäläinen, Jaakko Kaprio, Mari A. Kaunisto, Andrew C. Heath, Grant W. Montgomery, Hartmut Göbel, Unda Todt, Michel D. Ferrari, Lenore J. Launer, Rune R. Frants, Gisela M. Terwindt, Boukje de Vries, W. M. Monique Verschuren, Jan Brand & 14 muut Tobias Freilinger, Volker Pfaffenrath, Andreas Straube, Dennis G. Ballinger, Yiping Zhan, Mark J. Daly, David R. Cox, Martin Dichgans, Arn M. J. M. van den Maagdenberg, Christian Kubisch, Nicholas G. Martin, Maija Wessman, Leena Peltonen, Aarno Palotie

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    "The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out."
    Alkuperäiskielienglanti
    LehtiHuman Molecular Genetics
    Vuosikerta17
    Numero21
    Sivut3318-3331
    Sivumäärä14
    ISSN0964-6906
    DOI - pysyväislinkit
    TilaJulkaistu - 2008
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Tieteenalat

    • 311 Peruslääketieteet
    • 312 Kliiniset lääketieteet
    • 318 Lääketieteen bioteknologia
    • 217 Lääketieteen tekniikka
    • 118 Biotieteet
    • 314 Terveystieteet

    Lainaa tätä

    Nyholt, Dale R. ; LaForge, K. Steven ; Kallela, Mikko ; Alakurtti, Kirsi ; Anttila, Verneri ; Färkkilä, Markus ; Hämäläinen, Eija ; Kaprio, Jaakko ; Kaunisto, Mari A. ; Heath, Andrew C. ; Montgomery, Grant W. ; Göbel, Hartmut ; Todt, Unda ; Ferrari, Michel D. ; Launer, Lenore J. ; Frants, Rune R. ; Terwindt, Gisela M. ; de Vries, Boukje ; Verschuren, W. M. Monique ; Brand, Jan ; Freilinger, Tobias ; Pfaffenrath, Volker ; Straube, Andreas ; Ballinger, Dennis G. ; Zhan, Yiping ; Daly, Mark J. ; Cox, David R. ; Dichgans, Martin ; van den Maagdenberg, Arn M. J. M. ; Kubisch, Christian ; Martin, Nicholas G. ; Wessman, Maija ; Peltonen, Leena ; Palotie, Aarno. / A high-density association screen of 155 ion transport genes for involvement with common migraine. Julkaisussa: Human Molecular Genetics. 2008 ; Vuosikerta 17, Nro 21. Sivut 3318-3331.
    @article{de148cd5cd274e51b4f3225067d906d7,
    title = "A high-density association screen of 155 ion transport genes for involvement with common migraine",
    abstract = "{"}The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.{"}",
    keywords = "311 Basic medicine, 312 Clinical medicine, 318 Medical biotechnology, 217 Medical engineering, 118 Biological sciences, 314 Health sciences",
    author = "Nyholt, {Dale R.} and LaForge, {K. Steven} and Mikko Kallela and Kirsi Alakurtti and Verneri Anttila and Markus F{\"a}rkkil{\"a} and Eija H{\"a}m{\"a}l{\"a}inen and Jaakko Kaprio and Kaunisto, {Mari A.} and Heath, {Andrew C.} and Montgomery, {Grant W.} and Hartmut G{\"o}bel and Unda Todt and Ferrari, {Michel D.} and Launer, {Lenore J.} and Frants, {Rune R.} and Terwindt, {Gisela M.} and {de Vries}, Boukje and Verschuren, {W. M. Monique} and Jan Brand and Tobias Freilinger and Volker Pfaffenrath and Andreas Straube and Ballinger, {Dennis G.} and Yiping Zhan and Daly, {Mark J.} and Cox, {David R.} and Martin Dichgans and {van den Maagdenberg}, {Arn M. J. M.} and Christian Kubisch and Martin, {Nicholas G.} and Maija Wessman and Leena Peltonen and Aarno Palotie",
    year = "2008",
    doi = "10.1093/hmg/ddn227",
    language = "English",
    volume = "17",
    pages = "3318--3331",
    journal = "Human Molecular Genetics",
    issn = "0964-6906",
    publisher = "Oxford University Press",
    number = "21",

    }

    Nyholt, DR, LaForge, KS, Kallela, M, Alakurtti, K, Anttila, V, Färkkilä, M, Hämäläinen, E, Kaprio, J, Kaunisto, MA, Heath, AC, Montgomery, GW, Göbel, H, Todt, U, Ferrari, MD, Launer, LJ, Frants, RR, Terwindt, GM, de Vries, B, Verschuren, WMM, Brand, J, Freilinger, T, Pfaffenrath, V, Straube, A, Ballinger, DG, Zhan, Y, Daly, MJ, Cox, DR, Dichgans, M, van den Maagdenberg, AMJM, Kubisch, C, Martin, NG, Wessman, M, Peltonen, L & Palotie, A 2008, 'A high-density association screen of 155 ion transport genes for involvement with common migraine', Human Molecular Genetics, Vuosikerta 17, Nro 21, Sivut 3318-3331. https://doi.org/10.1093/hmg/ddn227

    A high-density association screen of 155 ion transport genes for involvement with common migraine. / Nyholt, Dale R.; LaForge, K. Steven; Kallela, Mikko; Alakurtti, Kirsi; Anttila, Verneri; Färkkilä, Markus; Hämäläinen, Eija; Kaprio, Jaakko; Kaunisto, Mari A.; Heath, Andrew C.; Montgomery, Grant W.; Göbel, Hartmut; Todt, Unda; Ferrari, Michel D.; Launer, Lenore J.; Frants, Rune R.; Terwindt, Gisela M.; de Vries, Boukje; Verschuren, W. M. Monique; Brand, Jan; Freilinger, Tobias; Pfaffenrath, Volker; Straube, Andreas; Ballinger, Dennis G.; Zhan, Yiping; Daly, Mark J.; Cox, David R.; Dichgans, Martin; van den Maagdenberg, Arn M. J. M.; Kubisch, Christian; Martin, Nicholas G.; Wessman, Maija; Peltonen, Leena; Palotie, Aarno.

    julkaisussa: Human Molecular Genetics, Vuosikerta 17, Nro 21, 2008, s. 3318-3331.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - A high-density association screen of 155 ion transport genes for involvement with common migraine

    AU - Nyholt, Dale R.

    AU - LaForge, K. Steven

    AU - Kallela, Mikko

    AU - Alakurtti, Kirsi

    AU - Anttila, Verneri

    AU - Färkkilä, Markus

    AU - Hämäläinen, Eija

    AU - Kaprio, Jaakko

    AU - Kaunisto, Mari A.

    AU - Heath, Andrew C.

    AU - Montgomery, Grant W.

    AU - Göbel, Hartmut

    AU - Todt, Unda

    AU - Ferrari, Michel D.

    AU - Launer, Lenore J.

    AU - Frants, Rune R.

    AU - Terwindt, Gisela M.

    AU - de Vries, Boukje

    AU - Verschuren, W. M. Monique

    AU - Brand, Jan

    AU - Freilinger, Tobias

    AU - Pfaffenrath, Volker

    AU - Straube, Andreas

    AU - Ballinger, Dennis G.

    AU - Zhan, Yiping

    AU - Daly, Mark J.

    AU - Cox, David R.

    AU - Dichgans, Martin

    AU - van den Maagdenberg, Arn M. J. M.

    AU - Kubisch, Christian

    AU - Martin, Nicholas G.

    AU - Wessman, Maija

    AU - Peltonen, Leena

    AU - Palotie, Aarno

    PY - 2008

    Y1 - 2008

    N2 - "The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out."

    AB - "The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out."

    KW - 311 Basic medicine

    KW - 312 Clinical medicine

    KW - 318 Medical biotechnology

    KW - 217 Medical engineering

    KW - 118 Biological sciences

    KW - 314 Health sciences

    U2 - 10.1093/hmg/ddn227

    DO - 10.1093/hmg/ddn227

    M3 - Article

    VL - 17

    SP - 3318

    EP - 3331

    JO - Human Molecular Genetics

    JF - Human Molecular Genetics

    SN - 0964-6906

    IS - 21

    ER -