Dataset Information

VRK2, a Candidate Gene for Psychiatric and Neurological Disorders.

ABSTRACT: Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 (VRK2) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 in VRK2 showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls, p = 3.43 × 10-8) and MDD (130,620 cases and 347,620 controls, p = 4.32 × 10-12) in European populations. This SNP was also genome-wide significantly associated with SCZ in Han Chinese population (12,083 cases and 24,097 controls, p = 3.78 × 10-13), and all associations were in the same direction of allelic effects. These studies highlight the potential roles of VRK2 in the central nervous system, and this gene therefore might be a good candidate to investigate the shared genetic and molecular basis between SCZ and MDD, as it is one of the few genes known to show genome-wide significant associations with both illnesses. Furthermore, the VRK2 gene was found to be involved in multiple other congenital deficits related to the malfunction of neurodevelopment, adding further support for the involvement of this gene in the pathogenesis of these neurological and psychiatric illnesses. While the precise function of VRK2 in these conditions remains unclear, preliminary evidence suggests that it may affect neuronal proliferation and migration via interacting with multiple essential signaling pathways involving other susceptibility genes/proteins for psychiatric disorders. Here, we have reviewed the recent progress of genetic and molecular studies of VRK2, with an emphasis on its role in psychiatric illnesses and neurological functions. We believe that attention to this important gene is necessary, and further investigations of VRK2 may provide hints into the underlying mechanisms of SCZ and MDD.

SUBMITTER: Li M

PROVIDER: S-EPMC6323383 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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<i>VRK2</i>, a Candidate Gene for Psychiatric and Neurological Disorders.

Li Ming M Yue Weihua W

Molecular neuropsychiatry 20181107 3

Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 (<i>VRK2</i>) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For ins ...[more]

PMID: 30643786

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Project description:The field of psychiatry is hampered by a lack of robust, reliable and valid biomarkers that can aid in objectively diagnosing patients and providing individualized treatment recommendations. Here we review and critically evaluate the evidence for the most promising biomarkers in the psychiatric neuroscience literature for autism spectrum disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder, major depression and bipolar disorder, and substance use disorders. Candidate biomarkers reviewed include various neuroimaging, genetic, molecular and peripheral assays, for the purposes of determining susceptibility or presence of illness, and predicting treatment response or safety. This review highlights a critical gap in the biomarker validation process. An enormous societal investment over the past 50 years has identified numerous candidate biomarkers. However, to date, the overwhelming majority of these measures have not been proven sufficiently reliable, valid and useful to be adopted clinically. It is time to consider whether strategic investments might break this impasse, focusing on a limited number of promising candidates to advance through a process of definitive testing for a specific indication. Some promising candidates for definitive testing include the N170 signal, an event-related brain potential measured using electroencephalography, for subgroup identification within autism spectrum disorder; striatal resting-state functional magnetic resonance imaging (fMRI) measures, such as the striatal connectivity index (SCI) and the functional striatal abnormalities (FSA) index, for prediction of treatment response in schizophrenia; error-related negativity (ERN), an electrophysiological index, for prediction of first onset of generalized anxiety disorder, and resting-state and structural brain connectomic measures for prediction of treatment response in social anxiety disorder. Alternate forms of classification may be useful for conceptualizing and testing potential biomarkers. Collaborative efforts allowing the inclusion of biosystems beyond genetics and neuroimaging are needed, and online remote acquisition of selected measures in a naturalistic setting using mobile health tools may significantly advance the field. Setting specific benchmarks for well-defined target application, along with development of appropriate funding and partnership mechanisms, would also be crucial. Finally, it should never be forgotten that, for a biomarker to be actionable, it will need to be clinically predictive at the individual level and viable in clinical settings.

Dataset Information

VRK2, a Candidate Gene for Psychiatric and Neurological Disorders.

Publications

<i>VRK2</i>, a Candidate Gene for Psychiatric and Neurological Disorders.

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