Functional gene networks reveal distinct mechanisms segregating in migraine families

Rasmussen, Anne Marie; Kogelman, Lisette J. A.; Kristensen, David M.; Chalmer, Mona Ameri; Olesen, Jes; Hansen, Thomas Folkmann

doi:10.1093/brain/awaa242

Cited by 27 publications

(18 citation statements)

References 85 publications

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“…WGCNA is a well-established method for studying biological networks and diseases (Rasmussen et al, 2020). Considering that GSE89632 had more comprehensive and complete data, we used GSE89632 to detect modules highly correlated with NAFLD, and WGCNA was performed using R package "WGCNA" and carried out on all genes.…”

Section: Weighted Gene Co-expression Network Analysismentioning

confidence: 99%

Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease

Zhou

Wang

et al. 2021

Front. Genet.

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Background: Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. However, the dysregulated gene expression for NAFLD is still poorly understood.Material and methods: We analyzed two public datasets (GSE48452 and GSE89632) to identify differentially expressed genes (DEGs) in NAFLD. Then, we performed a series of bioinformatics analyses to explore potential hub genes in NAFLD.Results: This study included 26 simple steatosis (SS), 34 nonalcoholic steatohepatitis (NASH), and 13 healthy controls (HC). We observed 6 up- and 19 down-regulated genes in SS, and 13 up- and 19 down-regulated genes in NASH compared with HC. Meanwhile, the overlapping pathways between SS and NASH were PI3K-Akt signaling pathway and pathways in cancer. Then, we screened out 10 hub genes by weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction (PPI) networks. Eventually, we found that CYP7A1/GINS2/PDLIM3 were associated with the prognosis of hepatocellular carcinoma (HCC) in the TCGA database.Conclusion: Although further validation is still needed, we provide useful and novel information to explore the potential candidate genes for NAFLD prognosis and therapeutic options.

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Section: Weighted Gene Co-expression Network Analysismentioning

confidence: 99%

Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease

Zhou

Wang

et al. 2021

Front. Genet.

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“…to prevent brain dysexcitability 55 . In this regard, it is interesting to note that most of the areas forming part of the networks analyzed by us were active, together with the hypothalamus, even during the pre-monitory phase of migraine 1 , and that, in migraine families, a gene module in the visual cortex can determine a complex genetic trait setting peculiar gene–gene interactions, transcriptomic, and gene-networking both at the cortical level and at the level of the neuroendocrine system 56 .…”

Section: Discussionmentioning

confidence: 83%

Hypothalamic structural integrity and temporal complexity of cortical information processing at rest in migraine without aura patients between attacks

Porcaro

Renzo

Tinelli

et al. 2021

Sci Rep

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The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi’s fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.

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“…Neuropsychiatric Disease and Treatment 2021:17 1184 signalling, and heterotrimeric G-protein signalling pathway-Gq alpha and Go alpha-mediated pathways, and furthermore identified the ATXN1, FAM153B and CACNA1B genes as being the most frequently mutated among migraine families. 38…”

Section: Dovepressmentioning

confidence: 99%

Exploring the Hereditary Nature of Migraine

Bron¹,

Sutherland²,

Griffiths³

2021

NDT

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Migraine is a common neurological disorder which affects 15-20% of the population; it has a high socioeconomic impact through treatment and loss of productivity. Current forms of diagnosis are primarily clinical and can be difficult owing to comorbidity and symptom overlap with other neurological disorders. As such, there is a need for better diagnostic tools in the form of genetic testing. Migraine is a complex disorder, encompassing various subtypes, and has a large genetic component. Genetic studies conducted on rare monogenic subtypes, including familial hemiplegic migraine, have led to insights into its pathogenesis via identification of causal mutations in three genes (CACNA1A, ATP1A2 and SCN1A) that are involved in transport of ions at synapses and glutamatergic transmission. Study of familial migraine with aura pedigrees has also revealed other causal genes for monogenic forms of migraine. With respect to the more common polygenic form of migraine, large genome-wide association studies have increased our understanding of the genes, pathways and mechanisms involved in susceptibility, which are largely involved in neuronal and vascular functions. Given the preponderance of female migraineurs (3:1), there is evidence to suggest that hormonal or X-linked components can also contribute to migraine, and the role of genetic variants in mitochondrial DNA in migraine has been another avenue of exploration. Epigenetic studies of migraine have shown links between hormonal variation and alterations in DNA methylation and gene expression. While there is an abundance of preliminary studies identifying many potentially causative migraine genes and pathways, more comprehensive genomic and functional analysis to better understand mechanisms may aid in better diagnostic and treatment outcomes.

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Functional gene networks reveal distinct mechanisms segregating in migraine families

Cited by 27 publications

References 85 publications

Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease

Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease

Hypothalamic structural integrity and temporal complexity of cortical information processing at rest in migraine without aura patients between attacks

Exploring the Hereditary Nature of Migraine

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