The search for migraine genes: an overview of current knowledge

Cell. Mol. Life Sci. 64 (2007) 331–344 1420-682X/07/030331-14 DOI 10.1007/s00018-006-5592-y © Birkhäuser Verlag, Basel, 2006

Cellular and Molecular Life Sciences

Review The search for migraine genes: an overview of current knowledge
N. J. Colson a, F. Fernandez a, R. A. Lea a, b and L. R. Griffiths a, * Genomics Research Centre, School of Medical Science, Griffith University, Gold Coast,Queensland (Australia), 9726, Fax: +61 7 55948908, e-mail: l.griffiths@griffith.edu.au b Institute of Environmental Science and Research, Wellington (New Zealand)
a

Received 16 December 2005; received after revision 9 October 2006; accepted 13 November 2006 Online First 22 December 2006 Abstract. Migraine is a complex familial condition that imparts a significant burden on society. There isevidence for a role of genetic factors in migraine, and elucidating the genetic basis of this disabling condition remains the focus of much research. In this review we discuss results of genetic studies to date, from the discovery of the role of neural ion channel gene mutations in familial hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the more common forms of migraine.The success of FHM regarding discovery of genetic defects associated with the disorder remains elusive in common migraine, and causative genes have not yet been identified. Thus we suggest additional approaches for analysing the genetic basis of this disorder. The continuing search for migraine genes may aid in a greater understanding of the mechanisms that underlie the disorder and potentiallylead to significant diagnostic and therapeutic applications.

Keywords. Migraine, gene, susceptibility, linkage, association. Introduction Migraine is a primary headache disorder characterised by recurrent attacks of disabling head pain, which may be accompanied by nausea and emesis, and in some sufferers, neurological disturbances. Migraine imparts a significant burden on society, both sociallyand financially. The World Health Organization has identified migraine among the world’s top 20 leading causes of disability, with an impact that extends far beyond individual suffering [1]. The lack of clear symptom definitions and precise diagnostic criteria has led to variability in diagnosis. In 1988 the Internal Headache Society published a system of classification with specific definitions ofmigraine syndromes. This system requires that certain attributes be present to establish a diagnosis for migraine headaches [2]. This classification has recently been up* Corresponding author.

dated [3]. The two most frequent subtypes are migraine with aura (MA), previously known as classic migraine, and migraine without aura (MO), previously known as common migraine. Migraine without aura,which occurs in ∼77% of migraineurs [4], is characterised by moderate to severe head pain that is generally unilateral and pulsating, and exacerbated by physical activity. Nausea, along with phonophobia and photophobia, may occur [3]. Migraine with aura, which occurs in ∼31% of sufferers [4], is classified by the existence of focal neurological symptoms preceding or accompanying the headache [3].Neurological symptoms may include focal paresthesia or weakness, visual or auditory hallucination, vertigo, fainting or a confusional episode. Some sufferers undergo a premonitory phase and a resolution phase, in which they may experience food cravings, depression, excessive yawning or hypo/hyperactivity [3]. Some individuals experience both types of attack during their life [4].

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N. J.Colson et al.

The search for migraine genes

Family and twin studies have provided evidence for a genetic component in migraine. In 1996 Russel et al. compared the risk of migraine in 44 families to the general population. It was found that first-degree relatives of probands with MO had a 1.9-fold increased risk of MO, and first-degree relatives of probands with MA had a 4fold increased risk...