Genome-Wide Association Study in Vestibular Neuritis: Involvement of the Host Factor for HSV-1 Replication

Rujescu, Dan; Hartmann, Annette M.; Giegling, Ina; Konte, Bettina; Herrling, Marko; Himmelein, Susanne; Strupp, Michael

doi:10.3389/fneur.2018.00591

Cited by 54 publications

(34 citation statements)

References 49 publications

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“…A genome-wide association study (GWAS) in 131 AUV patients and 2,609 controls was recently performed. 18 The authors noted that this was a very small number of cases for GWAS analysis, but found associations in regions that were considered to be involved in viral disorders and insulin metabolism. The findings also support the general notion of both viral and vascular contributions to AUV presentations.…”

Section: Acute Unilateral Vestibulopathy (Vestibular Neuritis)mentioning

confidence: 99%

Acute Vestibular Syndrome

Kerber

2020

Semin Neurol

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The acute vestibular syndrome (AVS) is a label for presentations of new-onset severe dizziness, vertigo, or imbalance, with examination findings of nystagmus or gait unsteadiness. The prototypical AVS presentation is the acute unilateral vestibulopathy due to vestibular neuritis. Stroke is also a serious concern in patients with AVS. Most other peripheral vestibular disorders present as episodic or chronic syndromes. In this article, the diagnostic considerations, exam findings, and management of AVS are reviewed.

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Section: Acute Unilateral Vestibulopathy (Vestibular Neuritis)mentioning

confidence: 99%

Acute Vestibular Syndrome

Kerber

2020

Semin Neurol

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“…Datasets were combined to get a sufficient number of controls. For GWAS analysis, selected patients and controls were extracted from the combined dataset after global quality control [21].…”

Section: Overviewmentioning

confidence: 99%

A Variation in FGF14 Is Associated with Downbeat Nystagmus in a Genome-Wide Association Study

et al. 2020

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Downbeat nystagmus (DBN) is a frequent form of acquired persisting central fixation nystagmus, often associated with other cerebellar ocular signs, such as saccadic smooth pursuit or gaze-holding deficits. Despite its distinct clinical features, the underlying etiology of DBN often remains unclear. Therefore, a genome-wide association study (GWAS) was conducted in 106 patients and 2609 healthy controls of European ancestry to identify genetic variants associated with DBN. A genome-wide significant association (p < 5 × 10 −8 ) with DBN was found for a variation on chromosome 13 located within the fibroblast growth factor 14 gene (FGF14). FGF14 is expressed in Purkinje cells (PCs) and a reduction leads to a decreased spontaneous firing rate and excitability of PCs, compatible with the pathophysiology of DBN. In addition, mutations in the FGF14 gene cause spinocerebellar ataxia type 27. Suggestive associations (p < 1 × 10 −05 ) could be detected for 15 additional LD-independent loci, one of which is also located in the FGF14 gene. An association of a region containing the dihydrofolate reductase (DHFR) and MutS Homolog 3 (MSH3) genes on chromosome 5 was slightly below the genome-wide significance threshold. DHFR is relevant for neuronal regulation, and a dysfunction is known to induce cerebellar damage. Among the remaining twelve suggestive associations, four genes (MAST4, TPPP, FTMT, and IDS) seem to be involved in cerebral pathological processes. Thus, this GWAS analysis has identified a potential genetic contribution to idiopathic DBN, including suggestive associations to several genes involved in postulated pathological mechanisms of DBN (i.e., impaired function of cerebellar PCs).

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“…All individuals included in this exploratory study were part of the PAGES sample 32 . All schizophrenia patients were recruited from the Munich area in Germany.…”

Section: Schizophrenia Patients and Healthy Controlsmentioning

confidence: 99%

Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function

et al. 2020

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βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens before it was detected in various brain regions of the mouse, including the hippocampus and the cerebral cortex. Mutations in the mouse Crybb2 gene lead to alterations of sensorimotor gating measured as prepulse inhibition (PPI) and reduced hippocampal size, combined with an altered number of parvalbumin-positive GABAergic interneurons. Decreased PPI and alterations of parvalbumin-positive interneurons are also endophenotypes that typically occur in schizophrenia. To verify the results found in mice, we genotyped 27 single nucleotide polymorphisms (SNPs) within the CRYBB2 gene and its flanking regions and investigated different schizophrenia typical endophenotypes in a sample of 510 schizophrenia patients and 1322 healthy controls. In the case-control study, no association with schizophrenia was found. However, 3 of the 4 investigated haplotype blocks indicated a decreased CRYBB2 mRNA expression. Two of these blocks were associated with poorer antisaccade task performance and altered working memory-linked functional magnetic resonance imaging signals. For the two haplotypes associated with antisaccade performance, suggestive evidence was found with visual memory and in addition, haplotype block 4 showed a nominally significant association with reduced sensorimotor gating, measured as P50 ratio. These results were not schizophrenia-specific, but could be detected in a combined sample of patients and healthy controls. This is the first study to demonstrate the importance of βB2-crystallin for antisaccade performance and memory function in humans and therefore provides implications for βB2-crystallin function in the human brain.

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Genome-Wide Association Study in Vestibular Neuritis: Involvement of the Host Factor for HSV-1 Replication

Cited by 54 publications

References 49 publications

Acute Vestibular Syndrome

Acute Vestibular Syndrome

A Variation in FGF14 Is Associated with Downbeat Nystagmus in a Genome-Wide Association Study

Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function

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