<i>NCOR2</i> is a novel candidate gene for migraine-epilepsy phenotype

Nuottamo, Marjo Eveliina; Häppölä, Paavo; Artto, Ville; Hautakangas, Heidi; Pirinen, Matti; Hiekkalinna, Tero; Ellonen, Pekka; Lepistö, Maija; Hämäläinen, Eija; Siren, Auli; Lehesjoki, Anna‐Elina; Kallela, Mikko; Palotie, Aarno; Kaunisto, Mari A.; Wessman, Maija

doi:10.1177/03331024211068065

Cited by 7 publications

(5 citation statements)

References 58 publications

(73 reference statements)

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“…This gene was higher in brain regions with a higher ReHo increment. NCOR2 mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access to basal transcription (Lee et al, 2022 ) and is a novel candidate gene for the migraine-epilepsy phenotype (Nuottamo et al, 2022 ). The higher expression level of NCOR2 may lead to a ReHo increment by having a more inhibitory effect on gene transcription in migraine.…”

Section: Discussionmentioning

confidence: 99%

Genetic mechanisms underlying local spontaneous brain activity in episodic migraine

Gui,

Lu,

et al. 2024

Front. Neurosci.

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Advances in neuroimaging techniques during the past few decades have captured impaired functional brain activity in migraine disorders, yet the molecular mechanisms accounting for its alterations in migraine remain largely unknown. A total of 27 patients with episodic migraine (EM) and 30 matched healthy controls (HCs) underwent resting-state functional and structural magnetic resonance imaging (MRI) scans. Regional homogeneity (ReHo), low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) of fMRI were compared between the two groups. Based on the Allen Human Brain Atlas and risk genes in migraine, we identified gene expression profiles associated with ReHo alterations in EM. Compared with HCs, patients with EM showed increased ReHo in the left orbital part of the superior frontal gyrus (P < 0.05, cluster-level FWE-corrected). The expression profiles of 16 genes were significantly correlated with ReHo alterations in EM (P < 0.05/5,013, Bonferroni corrected). These genes were mainly enriched for transcription regulation, synaptic transmission, energy metabolism, and migraine disorders. Furthermore, the neural activation was positively correlated with Hamilton Rating Scale for Anxiety (HAMA) scores. To test the stability of our results, we repeated our procedure by using ALFF and fALFF and found these results had a high degree of consistency. Overall, these findings not only demonstrated that regional brain activity was increased in patients with EM, which was associated with emotional regulation but also provided new insights into the genetic mechanisms underlying these changes in migraine.

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Section: Discussionmentioning

confidence: 99%

Genetic mechanisms underlying local spontaneous brain activity in episodic migraine

Gui,

Lu,

et al. 2024

Front. Neurosci.

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“…[8][9][10][11][12] The migraine comorbidity in epilepsy has been extensively examined. 13,14 The prevalence of migraine-like headaches in patients with seizure-related headaches varies among studies. 15, 16 A substantial association has been reported between migraine-like headaches and interictal migraines in seizure-related headaches.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and effects of headaches on quality of life in individuals with epilepsy in Çorum province of Turkey

ELİAÇIK,

AYKAÇ

2023

J Health Sci Med /JHSM /jhsm

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Aims: Varying headache prevalence rates have been reported in individuals with epilepsy in the literature. This study was investigate the frequency and types of headaches in individuals with epilepsy, and the impact of headaches on the clinical features and quality of life in this patient group. Methods: 150 individuals with epilepsy, 83 female and 67 male, were included in the study sample by random sampling method. Headaches were primarily defined as pre-ictal, ictal, and post-ictal headaches according to the temporal relationship with seizures. Headaches that were not temporally related to seizures were defined as inter-ictal headaches. Types and features of participants’ headaches were evaluated using the headache questionnaire consisting of 35 questions. Individuals’ quality of life was evaluated using the Quality of Life in Epilepsy Inventory (QOLIE-10). Results: Of the 150 participants included in the study, 73.33% had generalized, 20% focal, and 6.66% combined generalized focal epilepsy, and 41.33% had accompanying headache complaints. Of the participants with headaches, 35.48% were male and 64.51% were female. Inter-ictal headache, which was detected in 72.58% participants, was the most common type of headache. Tension and migrainous type headaches were more common among participants with inter-ictal headache, whereas migrainous type headaches were more common among participants with pre- and post-ictal headaches. There were statistically significant differences in the scores obtained from all three subscales of QOLIE-10 inventory between the participants with and without headache. Accordingly, quality of life was worse in the headache group than in the headache-free group (p

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“…A few recent studies in the field of migraine used NGS for a different approach. First, SNP genotyping followed by NGS was used for linkage, haplotype, and variant analyses within a single large Finnish migraine-epilepsy family and found an association between the epilepsy phenotype and the NCOR2 gene that colocalises with one of the migraine risk loci (53). Second, in a WES of 16 individuals, who developed numerous neurological- and concussion-related symptoms following minor head injuries of which seven had developed migraines following the injury, revealed possible mutations in various ion channel, neurotransmitter, and ubiquitin-related genes, but causality of any of them needs to be established (51).…”

Section: Next-generation Sequencing In Migrainementioning

confidence: 99%

Migraine genetics: Status and road forward

et al. 2023

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Background Migraine is considered a multifactorial genetic disorder. Different platforms and methods are used to unravel the genetic basis of migraine. Initially, linkage analysis in multigenerational families followed by Sanger sequencing of protein-coding parts (exons) of genes in the genomic region shared by affected family members identified high-effect risk DNA mutations for rare Mendelian forms of migraine, foremost hemiplegic migraine. More recently, genome-wide association studies testing millions of DNA variants in large groups of patients and controls have proven successful in identifying many dozens of low-effect risk DNA variants for the more common forms of migraine with the number of associated DNA variants increasing steadily with larger sample sizes. Currently, next-generation sequencing, utilising whole exome and whole genome sequence data, and other omics data are being used to facilitate their functional interpretation and the discovery of additional risk factors. Various methods and analysis tools, such as genetic correlation and causality analysis, are used to further characterise genetic risk factors. Findings We describe recent findings in genome-wide association studies and next-generation sequencing analysis in migraine. We show that the combined results of the two most recent and most powerful migraine genome-wide association studies have identified a total of 178 LD-independent ( r2 < 0.1) genome-wide significant single nucleotide polymorphisms (SNPs), of which 99 were unique to Hautakangas et al., 11 were unique to Choquet et al., and 68 were identified by both studies. When considering that Choquet et al. also identified three SNPs in a female-specific genome-wide association studies then these two recent studies identified 181 independent SNPs robustly associated with migraine. Cross-trait and causal analyses are beginning to identify and characterise specific biological factors that contribute to migraine risk and its comorbid conditions. Conclusion This review provides a timely update and overview of recent genetic findings in migraine.

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NCOR2 is a novel candidate gene for migraine-epilepsy phenotype

Cited by 7 publications

References 58 publications

Genetic mechanisms underlying local spontaneous brain activity in episodic migraine

Genetic mechanisms underlying local spontaneous brain activity in episodic migraine

Characteristics and effects of headaches on quality of life in individuals with epilepsy in Çorum province of Turkey

Migraine genetics: Status and road forward

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