Our findings provide important evidence for the establishment of CACNA1C as a susceptibility gene for schizophrenia across world populations, but its roles in the pathogenesis of schizophrenia need to be further investigated.
The objective was to study the association of two genes of voltage-gated ion channels (CACNA1C and KCNH2) with the functional modulation of the cortical networks measured with EEG and graph-theory parameter during a cognitive task, both in individuals with schizophrenia and healthy controls.
The risk gene CACNA1C is strongly implicated in the etiology of all major psychiatric disorders, such as depressive disorder, bipolar disorder, autism spectrum disorder, and schizophrenia.
Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women.
Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia.
Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.
We also found unprecedented evidence for epistasis (interaction between genetic polymorphisms) in the caudate nucleus, thalamus, and cingulate and temporal cortical activation; and CACNA1C up-regulation in SCZ and BD parietal cortices.
Taken together, results of this study suggested that rs2007044 could affect the activation of the left IFG, which was a possible brain mechanism underlying the association between CACNA1C gene polymorphism and schizophrenia.
These results indicate that genetic variation in CACNA1C may contribute to risk for schizophrenia and bipolar disorder by impacting behavioral flexibility, potentially through altered regulation of BDNF expression in the prefrontal cortex.
Common and rare variants of the CACNA1C voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD.
The CACNA1C gene is strongly implicated in the etiology of multiple major neuropsychiatric disorders, such as bipolar disorder, major depression, and schizophrenia, with cognitive deficits being a common feature.
Particular sequence variants of the 30-mer are associated with risk status at several flanking single-nucleotide polymorphisms in the third intron of CACNA1C that have previously been linked to BD and SCZ.
Regulatory characterisation of the schizophrenia-associated CACNA1C proximal promoter and the potential role for the transcription factor EZH2 in schizophrenia aetiology.
Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Ca<sub>v</sub>1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression.
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
Put in perspective, ZNF804A rs1344706, not only had a significant main effect, but its SZ-specific effects were two orders of magnitude more widespread than that of CACNA1Crs1006737.
In humans, CACNA1C has emerged as one of the most widely reproduced and prominent candidate risk genes for a range of neuropsychiatric disorders, including bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder.