Genomewide significant linkage to migrainous headache on chromosome 5q21
Nyholt, D.R., Morley, K. I., Ferreira, M. A., Medland, S. E., Boomsma, D. I., Heath, A. C., Merikangas, K. R., Montgomery, G. W., & Martin, N. G. (2005) Genomewide significant linkage to migrainous headache on chromosome 5q21. American Journal of Human Genetics, 77(3), pp. 500-12.
Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs (130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine.
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|Item Type:||Journal Article|
|Additional Information:||Nyholt, Dale R Morley, Katherine I Ferreira, Manuel A R Medland, Sarah E Boomsma, Dorret I Heath, Andrew C Merikangas, Kathleen R Montgomery, Grant W Martin, Nicholas G eng AA007535/AA/NIAAA NIH HHS/ AA013320/AA/NIAAA NIH HHS/ AA013326/AA/NIAAA NIH HHS/ AA014041/AA/NIAAA NIH HHS/ AA07728/AA/NIAAA NIH HHS/ AA10249/AA/NIAAA NIH HHS/ AA11998/AA/NIAAA NIH HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2005/08/05 09:00 Am J Hum Genet. 2005 Sep;77(3):500-12. Epub 2005 Jul 28.|
|Keywords:||Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 5/*genetics, Cohort Studies, Female, *Genetic Linkage, Genetic Predisposition to Disease/*genetics, *Genome, Human, Humans, Interviews as Topic, Male, Middle Aged, Migraine Disorders/*genetics/physiopathology, Photophobia/genetics, Sodium-Potassium-Exchanging ATPase/genetics, Twin Studies as Topic|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2005 The American Society of Human Genetics|
|Deposited On:||21 Jan 2016 04:59|
|Last Modified:||21 Jan 2016 04:59|
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