Common variants in the <i><scp>ARC</scp></i> gene are not associated with cognitive abilities

Myrum, Craig; Giddaluru, Sudheer; Jacobsen, Kaya Kvarme; Espeseth, Thomas; Nyberg, Lars; Lundervold, Astri J.; Haavik, Jan; Nilsson, Lars‐Göran; Reinvang, Ivar; Steen, Vidar M.; Johansson, Stefan; Wibrand, Karin; Hellard, Stéphanie Le; Bramham, Clive R.

doi:10.1002/brb3.376

Cited by 6 publications

(1 citation statement)

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“…In agreement, convergent genetic, molecular, clinical, neurophysiological, neuropsychological and imaging work confirmed the presence of an altered pattern of PFC and hippocampal activation in schizophrenia (Meyer-Lindenberg and Weinberger, 2006 ; Papaleo et al, 2012 ; Millan et al, 2014 ). Initial work did not find an association between Arc common genetic variants and general cognitive abilities in healthy subjects (Myrum et al, 2015b ). However, the Arc genetic variations investigated were not shown to have a functional impact on Arc protein or mRNA expression.…”

Section: Cognitive Systemsmentioning

confidence: 99%

Schizophrenia: What’s Arc Got to Do with It?

Managò

Papaleo

2017

Front. Behav. Neurosci.

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Human studies of schizophrenia are now reporting a previously unidentified genetic convergence on postsynaptic signaling complexes such as the activity-regulated cytoskeletal-associated (Arc) gene. However, because this evidence is still very recent, the neurobiological implication of Arc in schizophrenia is still scattered and unrecognized. Here, we first review current and developing findings connecting Arc in schizophrenia. We then highlight recent and previous findings from preclinical mouse models that elucidate how Arc genetic modifications might recapitulate schizophrenia-relevant behavioral phenotypes following the novel Research Domain Criteria (RDoC) framework. Building on this, we finally compare and evaluate several lines of evidence demonstrating that Arc genetics can alter both glutamatergic and dopaminergic systems in a very selective way, again consistent with molecular alterations characteristic of schizophrenia. Despite being only initial, accumulating and compelling data are showing that Arc might be one of the primary biological players in schizophrenia. Synaptic plasticity alterations in the genetic architecture of psychiatric disorders might be a rule, not an exception. Thus, we anticipate that additional evidence will soon emerge to clarify the Arc-dependent mechanisms involved in the psychiatric-related dysfunctional behavior.

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Section: Cognitive Systemsmentioning

confidence: 99%

Schizophrenia: What’s Arc Got to Do with It?

Managò

Papaleo

2017

Front. Behav. Neurosci.

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The Arc Gene Confers Genetic Susceptibility to Alzheimer’s Disease in Han Chinese

Kong

et al. 2017

Mol Neurobiol

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Alzheimer's disease (AD) is the most common form of dementia. The deposition of β-amyloid (Aβ) plaques in the brain was considered one of the main neuropathological hallmarks of AD. As the loss of synapses always occurs during AD progression, AD has been gradually regarded as a "synaptopathy." The activity-regulated cytoskeleton-associated protein (Arc) was recently identified as a key factor for AD due to its active roles in synaptic plasticity, learning, memory, and Aβ generation. However, there is little evidence to support the association of the Arc gene with AD. In this study, a two-stage case-control study of 1471 Han Chinese was conducted to investigate the genetic association between the Arc gene and AD. Variant rs10097505 in the 3'UTR region was significantly associated with AD. The whole exons of the Arc gene were also screened in 99 AD patients with a high heritability (familial and/or onset age <55 years old). One missense variant (c.20G>A, p.T7I) was identified in two AD patients but was absent in the controls from the general populations. Both rs10097505 and c.20G>A were predicted to be potentially pathogenic. Further luciferase assay, data mining, and integrative analyses revealed that the AD-risk genotype AA of rs10097505 was associated with an increased Arc mRNA expression and an elevated Aβ level. Our results indicated that the Arc gene would confer susceptibility to AD in Han Chinese, probably through changing the protein structure or affecting the Arc expression in brain tissues, which would finally contribute to the pathogenesis and development of AD.

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