Genetic and Environmental Influences on Migraine: A Twin Study Across Six Countries

Mulder, E.; Baal, Caroline van; Garcı́a-Dorado, David; Kallela, Mikko; Kaprio, Jaakko; Svensson, Dan A.; Nyholt, Dale R.; Martin, Nicholas G.; Macgregor, Alexander; Cherkas, Lynn; Boomsma, Dorret I.; Palotie, Aarno

doi:10.1375/136905203770326420

Cited by 293 publications

(92 citation statements)

References 42 publications

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“…While the power to detect genetic associations will be degraded by potential misclassification due to the heterogeneity of the clinical presentation, associations that are selective for migraine with certain characteristics may help reveal detailed biological causes of migraine, and anticipate the potential of gene-based migraine classification and treatment. Genetics is known to be an important determinant of migraine with heritability estimated in the range 30–60%; and the heritability for MA is estimated somewhat higher than for MO [6]–[10]. Recent reports have described a greater number of highly significant common genetic variants for MO than MA in genome-wide analyses, as well as only partial overlap between the sets of identified genes [11]–[13].…”

Section: Introductionmentioning

confidence: 99%

Selectivity in Genetic Association with Sub-classified Migraine in Women

et al. 2014

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Migraine 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.

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Section: Introductionmentioning

confidence: 99%

Selectivity in Genetic Association with Sub-classified Migraine in Women

et al. 2014

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“…Migraine pathophysiology involves both multiple genetic and environmental factors [19]. MTHFR 677C>T polymorphism (rs1801133) appear to play important roles in the vascular oxidative stress response [20].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Risk Related to MTHFR 677C>T Gene Polymorphism in Migraine Patients in Kashmiri Population

Pandith¹,

Wani²,

Qasim³

et al. 2017

OJPM

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“…Migraine is a complex multifactorial neurologic disorder, in which genetic factors explain about 46% of the risk with the remaining 54% of the variability related to environmental factors (Mulder et al 2003). Recent genome wide association studies (GWAS) have successfully identified several genetic susceptibility loci for migraine (Anttila et al 2013; Gormley et al 2016) but much less is known of which genetic variants operate in the presence of a given environmental effect (Eising et al 2013b).…”

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Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

Juhász

Csépány

Magyar

et al. 2016

Genes Brain and Behavior

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One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross‐sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID‐Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression‐ and anxiety‐related phenotypes. In addition, a Bayesian systems‐based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

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Genetic and Environmental Influences on Migraine: A Twin Study Across Six Countries

Cited by 293 publications

References 42 publications

Selectivity in Genetic Association with Sub-classified Migraine in Women

Selectivity in Genetic Association with Sub-classified Migraine in Women

Evaluation of Risk Related to MTHFR 677C>T Gene Polymorphism in Migraine Patients in Kashmiri Population

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

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Genetic and Environmental Influences on Migraine: A Twin Study Across Six Countries

Cited by 293 publications

References 42 publications

Selectivity in Genetic Association with Sub-classified Migraine in Women

Selectivity in Genetic Association with Sub-classified Migraine in Women

Evaluation of Risk Related to MTHFR 677C&gt;T Gene Polymorphism in Migraine Patients in Kashmiri Population

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

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Evaluation of Risk Related to MTHFR 677C>T Gene Polymorphism in Migraine Patients in Kashmiri Population