Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder.
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.
Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.
The single nucleotide polymorphism at rs1006737 in CACNA1C has been associated with both schizophrenia and bipolar disorder and with several intermediate phenotypes that may serve as neurobiological antecedents, linking psychosis to genetic aetiology.
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.
On the other hand, our results indicate that alterations in the functional coupling between the prefrontal cortex and the medial temporal lobe could represent a neural system phenotype that is mediated by CACNA1Crs1006737 and other genetic susceptibility loci for schizophrenia and bipolar disorder.
The rs10994336 ANK3 and rs1006737CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression.
Since CACNA1C variants have been associated repeatedly with psychosis at a genome-wide level, and preclinical data provide convergent evidence for the relevance of the CACNA1C gene for hippocampal and frontolimbic plasticity and adaptive regulation of stress, our data suggest a potential pathophysiological mechanism conferred by CACNA1C variants that may mediate risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia.
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 ZNF804A and CACNA1C loci appear to influence risk for both disorders, a finding that supports the hypothesis that schizophrenia and BD are not aetiologically distinct.
Strong genetic associations have been reported at common polymorphisms within ANK3 and CACNA1C in bipolar disorder and ZNF804A in schizophrenia and a relatively specific association between common variation in GABA(A) receptor genes and cases with features of both bipolar disorder and schizophrenia.
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.
In conclusion, polymorphisms in CACNA1C and SYNE1 could confer a greater risk of developing SZ and BD in individuals who are already at high risk because of their family history.
Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women.
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.