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 Vol 10: Selectivity in Genetic Association with Sub-classified Migraine in Women.


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This article is from PLoS Genetics, volume 10.AbstractMigraine can be sub-classified not only according to presence of migraine aura MA or absence of migraine aura MO, but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies GWAS have identified 12 independent loci at which single nucleotide polymorphisms SNPs are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 LRP1 for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 near TGFBR2 and rs2274316 MEF2D were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 TRPM8 was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine.



Autor: Chasman, Daniel I.; Anttila, Verneri; Buring, Julie E.; Ridker, Paul M.; Schurks, Markus; Kurth, Tobias

Fuente: https://archive.org/







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