A genome-wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Ligthart, Lannie, Nyholt, Dale R., Hottenga, Jouke-Jan, Distel, Marijn A., Willemsen, Gonneke, & Boomsma, Dorret I. (2008) A genome-wide linkage scan provides evidence for both new and previously reported loci influencing common migraine. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B(7), pp. 1186-1195.

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Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N = 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genome-wide linkage analysis was performed using genotype data from 105 families with at least 2 affected siblings. In addition to this primary phenotype, linkage analyses were performed for the individual migraine symptoms. Significance levels, corrected for the analysis of multiple traits, were determined empirically via a novel simulation approach. Suggestive linkage for migrainous headache was found on chromosomes 1 (LOD = 1.63; pointwise P = 0.0031), 13 (LOD = 1.63; P = 0.0031), and 20 (LOD = 1.85; P = 0.0018). Interestingly, the chromosome 1 peak was located close to the ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2). Individual symptom analysis produced a LOD score of 1.97 (P = 0.0013) on chromosome 5 (photo/phonophobia), a LOD score of 2.13 (P = 0.0009) on chromosome 10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P = 0.00005) on chromosome 13 (pulsating headache). These peaks were all located near regions previously reported in migraine linkage studies. Our results provide important replication and support for the presence of migraine susceptibility genes within these regions, and further support the utility of an LCA-based phenotyping approach and analysis of individual symptoms in migraine genetic research. Additionally, our novel "2-step" analysis and simulation approach provides a powerful means to investigate linkage to individual trait components.

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ID Code: 92099
Item Type: Journal Article
Refereed: Yes
Keywords: Adolescent, Adult, Aged, Aged, 80 and over, Chromosomes, Human, Family Health, Female, *Genetic Linkage, Genetic Predisposition to Disease, *Genome, Human, Genomics/methods, Genotype, Humans, Lod Score, Male, Middle Aged, Migraine without Aura/*genetics, Netherlands/epidemiology, Siblings
DOI: 10.1002/ajmg.b.30749
ISSN: 1552-485X
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 20 Jan 2016 00:53
Last Modified: 12 Feb 2016 01:17

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