A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine

• Published in: Neurogenetics Vol. 6; no. 2; pp. 67 - 72
• Main Authors: Lea, R. A., Nyholt, D. R., Curtain, R. P., Ovcaric, M., Sciascia, R., Bellis, C., MacMillan, J., Quinlan, S., Gibson, R. A., McCarthy, L. C., Riley, J. H., Smithies, Y. J., Kinrade, S., Griffiths, L. R.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2005; Springer Nature B.V
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 18; Gene Expression Profiling; Gene loci; General aspects. Genetic counseling; Genetic Linkage; Genetic Predisposition to Disease; Genomics; Heredity; Humans; Medical genetics; Medical sciences; Migraine; Migraine without Aura - genetics; Neurology; Pedigree; Phenotype; Vascular diseases and vascular malformations of the nervous system; Nervous system diseases; Pathogenesis; Susceptibility; Migraine; Cardiovascular disease; Genome scan; Genetic determinism; Loci; Cerebral disorder; Vascular disease; Sensitivity; Pain; Central nervous system disease; Predisposition; Genetics; Severe; Genome; Locus; Cerebrovascular disease
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s10048-005-0215-6

Migraine is a prevalent neurovascular disease with a significant genetic component. Linkage studies have so far identified migraine susceptibility loci on chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92 Australian pedigrees phenotyped for migraine with and without aura and for a more heritable form of "severe" migraine. Multipoint non-parametric linkage analysis revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype (LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele sharing was also observed at multiple different chromosomal regions, some of which overlap with, or are directly adjacent to, previously implicated migraine susceptibility regions. We have provided evidence for two loci involved in severe migraine susceptibility and conclude that dissection of the "migraine" phenotype may be helpful for identifying susceptibility genes that influence the more heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded that the genetic aetiology of the common (International Headache Society) forms of the disease is probably comprised of a number of low to moderate effect susceptibility genes, perhaps acting synergistically, and this effect is not easily detected by traditional single-locus linkage analyses of large samples of affected pedigrees.