The impact of CACNA1C allelic variation on regional gray matter volume in Chinese population

Huang, Liang; Mo, Yin; Sun, Xiaochuan; Yu, Hualin; Li, Hao; Wu, Lian; Li, Ming

doi:10.1002/ajmg.b.32418

Cited by 11 publications

(7 citation statements)

References 48 publications

(51 reference statements)

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“…10,11 Among these characteristics, the risk allele of rs1006737 polymorphism in the CACNA1C gene is of particular interest because it is associated with a positive effect in grey matter (GM) density. 10,12,13 CACNA1C is a gene that encodes for the transmembrane α 1C subunit of the L-type voltage-gated calcium channel (LTCC) nominated Ca V 1.2, which facilitate transient activation of inward calcium that regulates the transcription of calcium-dependent genes with neurotropic functions such as brain-derived neurotrophic factor (BDNF). 10,14 A single nucleotide polymorphism (SNP) of CACNA1C has been associated with BD with genomewide significance, the risk variant consists in the presence of the A allele of rs1006737.…”

Section: Introductionmentioning

confidence: 99%

CACNA1C Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder

Rodríguez-Ramírez¹,

Meza-Urzúa²,

Cedillo-Ríos³

et al. 2020

NDT

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Purpose: Bipolar disorder (BD) is a condition associated with structural alterations in the prefrontal cortex (PFC); some genetic variants and mood stabilizer medications like lithium or valproate are associated with these changes. CACNA1C is a gene involved in BD pathology and brain function; carriers of the A allele of rs1006737 are reported to have increased risk for BD and increased cortical thickness (CT) in the PFC compared to noncarriers. Lithium is also associated with increased CT in the PFC of BD subjects compared to the ones on valproate. The influence of these treatments and gene variants over the PFC structure of Mexican subjects has not been explored. Therefore, we evaluate the effects of mood stabilizers and risk A allele of CACNA1C rs1006737 on the prefrontal cortical thickness of Mexican BD patients treated with lithium or valproate. Patients and Methods: A cross-sectional study of 40 BD type I euthymic adult outpatients (20 treated with lithium and 20 with valproate) who underwent a 3T T1-weighted 3D brain scan and genotyping for CACNA1C risk allele rs1006737 was conducted. We performed a cortical thickness analysis of the dorsolateral and orbitofrontal regions of the prefrontal cortex with BrainVoyager 20.6. The effects of treatment and gene variants were analyzed with a two-way multivariate analysis of covariance. Results: There was no association of CACNA1C risk allele rs1006737 with CT measures of both PFCs nor significant interaction between the genetic variant and treatment. Mood stabilizers reported the main effect on the CT measures of the right PFC of our sample. Patients on treatment with lithium showed higher mean CT on the right orbitofrontal cortex. Conclusion: We did not find any association between the prefrontal CT and CACNA1C risk A allele rs1006737 in BD Mexican patients treated with lithium or valproate. Our results suggest that mood stabilizers had the main effect in the CT of the right PFC.

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Section: Introductionmentioning

confidence: 99%

CACNA1C Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder

Rodríguez-Ramírez¹,

Meza-Urzúa²,

Cedillo-Ríos³

et al. 2020

NDT

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“…Unlike rs1006737, rs2007044 has approximate MAFs between different ethnic populations. Moreover, the results of the effects of rs1006737 on cortical morphology were inconsistent, with some reporting changes in regional cortical volume 43 44 while others finding no difference in either the regional cortical volume or the subcortical grey matter volume 45 46 . It is worth noting that cortical volume comprises both surface area and thickness, and previous studies suggested that these two components of cortical volume are genetically and phenotypically independent 17 47 .…”

Section: Discussionmentioning

confidence: 99%

The effects of a genome-wide supported variant in the CACNA1C gene on cortical morphology in schizophrenia patients and healthy subjects

Zheng

Cui

Yan

et al. 2016

Sci Rep

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Schizophrenia is a highly heritable disorder with multiple susceptibility genes. Previously, we identified CACNA1C rs2007044 as a new risk locus for schizophrenia, with the minor allele G as risk allele. This association was recently validated by a powerful genome-wide association study. However, the underlying neural mechanisms remain unclear. Therefore, we tested whether the risk allele has an influence on cortical surface area and thickness in a sample of schizophrenia patients and healthy controls. We found significant genotype by diagnosis interactions on cortical surface area, but not thickness, in the right dorsolateral prefrontal cortex and the left superior parietal cortex, both of which are key components of the central executive network. Moreover, the surface areas of both regions were inversely correlated with PANSS negative scores in AA homogeneous patients but not in G-carriers. This is the first study to describe the influence of the new genome-wide supported schizophrenia risk variant on cortical morphology. Our data revealed a significant genetic effect of cortical surface area in pivotal brain regions, which have been implicated in the pathophysiology of schizophrenia, possibly via their involvement in cognitive functions. These results yield new insights into the potential neural mechanisms linking CACNA1C to the risk of schizophrenia.

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“…Among the common SNP variants identified from the recent GWAS for example, variations in CACNA1C have been implicated as calcium signaling SNPs, found to confer the risk for schizophrenia [ 62 ]. Addressing this, several studies analyzed the calcium voltage-gated channel subunit α1 C-gene (CACNA1C) variations by the use of electrophysiological endophenotypes assessing phases of sleep in infants [ 64 ] by measuring regional gray matter volume [ 65 ], by measuring amygdale structure and/or function [ 66 , 67 ] by proton magnetic resonance spectroscopy of glutamatergic signals [ 68 ]. In the meanwhile, animal studies generate conditional knock-out mice for the analysis of calcium signaling in cellular level, linked to neuropsychiatric diseases [ 69 , 70 ].…”

Section: The New Agementioning

confidence: 99%

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

Arslan

2018

IJMS

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Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ.

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The impact of CACNA1C allelic variation on regional gray matter volume in Chinese population

Cited by 11 publications

References 48 publications

<p><em>CACNA1C</em> Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder</p>

<p><em>CACNA1C</em> Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder</p>

The effects of a genome-wide supported variant in the CACNA1C gene on cortical morphology in schizophrenia patients and healthy subjects

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

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