Group Wessman

Migraine and Migraine-Epilepsy

We aim to identify susceptibility variants that may affect both the development of migraine and migraine-epilepsy. Understanding the molecular mechanisms that precede and give rise to a migraine/migraine-epilepsy attack may help to develop new therapeutic strategies.

The two main phases of a migraine attack are the aura phase and the headache that follows. In most cases aura is visual but it can also be motor weakness, as in the case of hemiplegic migraine (HM). To date high-penetrance causal variants have been identified only for HM in three ion transport genes. Mutations in these genes have also been shown to cause epilepsy that is one of the several comorbid disorders with migraine.

Our goal is to identify susceptibility variants for migraine visual and motor aura and migraine-epilepsy in our large Finnish migraine family collection of 2 300 families with 11 000 family members collected nationwide.

We have identified visual migraine aura and migraine-epilepsy loci in chromosomes 9, 12 and 14 and are studying these loci further using exome and targeted sequencing approaches. Our recent large-scale GWA meta-analyses of 375 000 individuals, within the International Headache Genetics Consortium, lead by Prof. Aarno Palotie, identified 38 migraine loci. Interestingly, the loci are enriched for genes that are expressed most actively in arterial tissue.

We are also involved in an international consortia studying episodic and chronic migraine.

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Senior Scientists

Ville Artto, MD, PhD

Mari Kaunisto, PhD

Graduate Students

Marjo Hiekkala, MSc

Salli Vepsäläinen, MD, Neurologist

Staff

Leena Leikas, Research Nurse

1. Kallela M, Wessman M, Färkkilä, M, Palotie A, Koskenvuo M, Honkasalo, M-L, Kaprio J: Clinical characteristics of migraine in a population-based twin sample: differences in headache between migraine with and without aura. Cephalalgia, 19:151-158, 1999.

2. Wessman M, Kallela M, Kaunisto M, Marttila P, Sobel E, Hartiala J, Oswell G, Leal S, Papp J, Hämäläinen E, Broas P, Joslyn G, Hovatta I, Hiekkalinna T, Kaprio J, Ott J, Cantor R, Zwart J-A, Ilmavirta M, Havanka H, Färkkilä M, Peltonen L, Palotie A. A Susceptibility Locus for Migraine with Aura, on Chromosome 4q24. Am J Hum Genet 70:652-662, 2002

3. Kaunisto MA, Harno H,Vanmolkot,KRJ.,Gargus JJ, Sun G, Liukkonen E, Kallela M,Van Den Maagdenberg AMJM, Frants RR, Palotie A, Färkkilä M, Wessman M. A novel missense ATP1A2 mutation in a large Finnish family with familial hemiplegic migraine type 2. Neurogenetics 5: 141-146, 2004

4. Anttila V, Kallela M, Oswell G, Kaunisto M, Nyholt D, Hämäläinen E, Terwilliger J, Sobel E, Kaprio J, Färkkilä M, Wessman M, Palotie A. Trait component analysis of migraine families reveals two new loci. Am J Hum Genet 79: 85-99, 2006

5. Anttila V, Nyholt DR, Kallela M, Artto V, Vepsäläinen S, Wennerström A, Tikka-Kleemola P, Kaunisto MA, Hämäläinen E, Widén E, Terwilliger J, Merikangas K, Montgomery DW, Martin NG, Kaprio J, Peltonen L, Färkkilä M, Wessman M, Palotie A. Chromosome 10q21-q23 – a consistently replicating locus for migraine. Am J Hum Genet, 82(5):1051-1063, 2008

6. Tikka-Kleemola P, Artto V, Vepsäläinen S, Sobel E, Räty S, Kaunisto MA, Anttila V, Hämäläinen E, Sumelahti M-L, Ilmavirta M, Färkkilä M, Kallela M, Palotie A, Wessman M. A visual migraine aura locus maps to 9q21-q22. Neurology 74(15):1171-1177, 2010

7. Anttila V, Stefansson H, Kallela M, Todt U, Terwindt GM, Calafato MS, Nyholt DR, Dimas AS, Freilinger T, Müller-Myhsok B, Artto V, Inouye M, Alakurtti K, Kaunisto MA, Hämäläinen E, de Vries B, Stam AH, Weller CM, Heinze A, Heinze-Kuhn K, Goebel I, Borck G, Göbel H, Steinberg S, Wolf C, Björnsson 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, Vepsäläinen S, Lucae S, Tozzi F, Muglia P, Barrett J, Kaprio J, Färkkilä 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 Consortium. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet 42(10):869-873, 2010

8. Polvi A, Siren A, Kallela M, Rantala H, Artto V, Sobel EM, Palotie A, Lehesjoki AE, Wessman M. Shared loci for migraine and epilepsy on chromosomes 14q12-q23 and 12q24.2-24.3. Neurology, 78(3):202-209, 2012

9. Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, Kallela M, Malik R, de Vries B, Terwindt G, Medland SE, Todt U, McArdle WL, Quaye L, Koiranen M, Ikram MA, Lehtimäki T, Stam AH, Ligthart L, Wedenoja J, Dunham I,Neale BM, Palta P, Hamalainen E, Schürks M, Rose LM, Buring JE, Ridker PM,Steinberg S, Stefansson H, Jakobsson F, Lawlor DA, Evans DM, Ring SM, Färkkilä M,Artto V, Kaunisto MA, Freilinger T, Schoenen J, Frants RR, Pelzer N, Weller CM,Zielman R, Heath AC, Madden PA, Montgomery GW, Martin NG, Borck G, Göbel H,Heinze A, Heinze-Kuhn K, Williams FM, Hartikainen AL, Pouta A, van den Ende J,Uitterlinden AG, Hofman A, Amin N, Hottenga JJ, Vink JM, Heikkilä K, Alexander M,Muller-Myhsok B, Schreiber S, Meitinger T, Wichmann HE, Aromaa A, Eriksson JG,Traynor BJ, Trabzuni D, Rossin E, Lage K, Jacobs SB, Gibbs JR, Birney E, Kaprio J, Penninx BW, Boomsma DI, van Duijn C, Raitakari O, Jarvelin MR, Zwart JA,Cherkas L, Strachan DP, Kubisch C, Ferrari MD, van den Maagdenberg AM, Dichgans M, Wessman M, Smith GD, Stefansson K, Daly MJ, Nyholt DR, Chasman DI, Palotie A; North American Brain Expression Consortium; UK Brain Expression Consortium; International Headache Genetics Consortium. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat Genet 45(8):912-917, 2013

10. 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, Lehtimäki T, Sarin AP, Wedenoja J, Hinds DA, Buring JE, Schürks M, Ridker PM, Hrafnsdottir MG, Stefansson H, Ring SM, Hottenga JJ, Penninx BW, Färkkilä M, Artto V, Kaunisto M, Vepsäläinen S, Malik R, Heath AC, Madden PA, Martin NG, Montgomery GW, Kurki MI, Kals M, Mägi R, Pärn K, Hämäläinen 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, Heikkilä K, Loehrer E, Uitterlinden AG, Hofman A, van Duijn CM, Cherkas L, Pedersen LM, Stubhaug A, Nielsen CS, Männikkö M, Mihailov E, Milani L, Göbel H, Esserlind AL, Christensen AF, Hansen TF, Werge T; International Headache Genetics Consortium, Kaprio J, Aromaa AJ, Raitakari O, Ikram MA, Spector T, Järvelin 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. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet 48(8):856-866, 2016

Folkhälsan Research Foundation

EVO Governmental Grants

European Commission

The Academy of Finland

Medicinska Understödsföreningen Liv och Hälsa (“Life and Health Medical Fund”)

Prof. Markus Färkkilä, Helsinki University Central Hospital, Helsinki, Finland

Prof. Aarno Palotie, Institute for Molecular Medicine Finland (FIMM) and Broad Institute of MIT and Harvard, Cambridge, USA/Head of the International Headache Genetics Consortium

Prof. Jaakko Kaprio, FIMM, Helsinki, Finland

Prof. John-Anker Zwart, Oslo University Hospital, Norway

Prof. Dale Nyholt, Queensland University of Technology, Australia

Prof. Arn van den Maagdenberg, Leiden University Medical Center, the Netherlands/coordinator of the EUROHEADPAIN Consortia

Prof. Eric Sobel, UCLA, Los Angeles, USA

Dr. Tero Hiekkalinna, National Institute for Health and Welfare (THL), Helsinki, Finland

Contact

    • Maija Wessman

      PhD, Docent, Group Leader

    • phn:

    • Folkhälsan Research Center P.O. Box 63, FI-00014 University of Helsinki

    • Contact
    • Mikko Kallela

      MD, PhD, Docent, Co-PI

    • phn:

    • Folkhälsan Research Center and Folkhälsan Institute of Genetics Biomedicum Helsinki P.O. Box 63, FI-00014 University of Helsinki

    • Contact