POSTER NO: 465

A Susceptibility Locus for Migraine with Aura on Chromosome 4q24

¹M. Wessman, ⁴M. Kallela, ¹G. Oswell, ³M. Kaunisto, ²J. Hartiala, ²P. Broas, ²E. Hamalainen, ²P. Marttila, ²T. Hiekkalinna, ²G. Joslyn, ²J. Papp, ⁵S.M. Leal, ²R. Cantor, ²E. Sobel, ⁵J. Ott, ⁶H. Havanka, ⁴M. Farkkila, ²L. Peltonen, ¹A. Palotie
¹Dept of Pathology, UCLA, Los Angeles, USA, ²Dept. of Human Genetics, UCLA, Los Angeles, USA, ³Dept. of Biosciences, Univ. of Helsinki, Helsinki, Finland, ⁴Dept. of Neurolgy, Univ. of Helsinki, Helsinki, Finland, ⁵Lab. of Statistical Genetics, Rockefeller Univ., New York, USA, ⁶Dept. of Neurology, Lansi Pohjan Hospital, Kemi, Finland

Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Migraine has two main types: migraine without aura (MO) occurring in 85% of patients and migraine with aura (MA) occurring in 15% of patients. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence for linkage or association. To date, no genome-wide screen for migraine has been published. We report results from a genome-wide screen on 50 multi-generational, clinically well-defined, Finnish families showing transmission from generation to generation of MA. The families were screened with 350 polymorphic microsatellite markers, with an average intermarker distance of 11cM. Significant evidence of linkage was found between the MA phenotype and the marker D4S1647 on chromosome 4q24. Using parametric two-point linkage analysis, assuming a dominant mode of inheritance, and allowing for locus heterogeneity, the maximum lod was 4.20 (under homogeneity p=0.000006). Multipoint parametric (HLOD = 4.45, p=0.0000058) and non-parametric (NPL-all = 3.43, p=0.0007) analyses support this finding. Statistically significant linkage was not observed in any other chromosomal region