Linkage Analysis of Calcium Channel Genes in Typical Migraine Families. R.A Lea¹, D.R Nyholt², R.P Curtain¹, K.L Jordan¹, L.R Griffiths¹. 1) Genomics Res Ctr, Sch Hlth Sci, Griffith University-Gold Coast, Southport QLD, Australia; 2) Laboratory of Statistical Genetics, Rockefeller University, New York.

   Migraine is a prevalent neurological disorder characterised by recurrent attacks of debilitating headache. The disease is genetically heterogeneous although the type and number of genes involved is still unknown. Mutations in the neuronal calcium channel gene (CACNA1A) have been shown to cause FHM, a rare and severe subtype of migraine [1]. Independent linkage analyses suggest that there are two FHM loci on chromosome 1 near the calcium channel genes CACNA1E and CACNA1S [2,3]. These findings suggest that calcium channel genes may also be involved in the more common types of migraine (with and without aura). We have previously reported linkage to CACNA1A in a large typical migraine family [4] and are currently performing linkage analyses on markers located in other calcium channel gene regions. 108 migraine families including 8 large multigenerational pedigrees have been genotyped for markers spanning the FHM implicated loci on chromosome 1 and results analysed using the GENEHUNTER-PLUS program. Although one large multigenerational family displayed some excess allele sharing, multipoint analysis of combined results significantly excluded the markers surrounding CACNA1S and CACNA1E (LOD < 2). These results indicate that if this locus plays a role in migraine it probably contributes only a small genetic effect to the disease. Other neuronal calcium channel gene markers located across the genome are currently being investigated in our migraine families. 1. Ophoff et al (1996). Cell;87:543-552 2. Gardener et al (1997). Neurology;47:1231-1238 3. Ducros et al (1997). Ann Neurol;42:885-890 4. Nyholt et al (1998). Neurology;50:1428-1432.