(1) In short, Gene Ontology analysis has identified several potentially affected pathways involved in synaptic transmission (HTR2A, BDNF, CHRNA3, CHRNB4, DRD1, DRD2, DRD4, EGR1, GRIA4, GRIN2B, GRM3, NISCH, SLC1A3, and ERBB4), dopamine metabolic processes (COMT, DRD1, DRD2, DRD4, MAOA, NR4A2, and SLC6A3), and ion channel activity (CHRNA7, CACNA1I, CACNB2
, CHRNA3, CHRNA5, CHRNB4, GABRB3, GRIA4, GRIA1, GRIN2B, HCN1, CACNA1C, KCTD13, KCNV1, KCNN3, KCNJ13, and KCNB1).
Several SNPs in genes involved with ion transport have been associated with blood pressure (e.g., ATP2B1, CACNA1D, CACNA2D2, CACNB2
, KCNK3, SLC4A7, and SLC39A8; Table 1).
Six other genes (CACNA1C, CACNB2
, SCN1B, KCNQ3, SCN3B, and HCN4) have been associated with BrS, but the prevalence of variants in these genes is yet unknown (6).
miRNA Target Partial target genes numbers miR-2070-3p 1352 SH3D21, BCL7C, ACTR3B, EPC1 miR-222 624 RGS6, HMG20A, RBM15, NFE2 miR-502-3p 462 CRTC1, FGD1, CCL8, STARD8 miR-6238 391 Mcph1, PDZK1 miR-7446-3p 414 KLF13, SIAH2, TUB miR-7475-5p 517 LDB1, DVL3, PEG3, LRP1, LATS2, EFHD2 miR-125a-5p 2246 ESRRa, SENP2, BCL2L12, SREBP-1, ABCA2, NNMT miR-126 2438 TNKS2, PTPRU, RGS14, NAP1L5 miR-378e 1044 IGF1R, CACNB2
, RASIP1, API5, SCD5, SLC25A29 miR-7930-3p 1793 CABIN1, PCDHA2, PLXNA4
These mutations include but are not limited to the SCN5A, GPD1-L, CACNA1C, CACNB2
, SCN1B, KCNE3, SCN3B, and HCN4genes (5).
Disease or Function p-Value Molecules # Mole Annotation cules Mood disorders 3.73E--04 ADRA2B, ALOX12, AQP4, CA9, 22 CACNB2
, CCKBR, CHRNA1, CHR NB4, CHRNG, DDC, ESR1, GRIA3, GRIK2, GRIN1, KCNK2, MTNR 1A, MYOM1, NCAM1, NDUFS7, PDE11A, SCN11A, SCN2B Depressive disorder 7.90E--04 ADRA2B, AQP4, CACNB2
, 14 CCKBR, CHRNA1, CHRNB4, CHRNG, ESR1, GRIA3, GRIN1, KCNK2, MYOM1, NCAM1, PDE11A Table 3 Effect of Rhodiola on genes involved in depression ([section]).
 A recent cross-disorder genomewide association study found similar genetic sensitivities in these five diagnostically distinct disorders on regions of chromosomes 3p21 and 10q24 and single-nucleotide polymorphisms (SNPs) within two genes that encode L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2
.  The specific SNPs were correlated with the age of onset of various mental illnesses, and polymorphism of the calcium-channel activity gene in the five disorders suggests that this gene is important in the onset of all of these conditions.
These loci harbored two gap junction-related genes, plakophilin 2 (PKP2) and cortactin-binding protein 2 Nterminal like (CTTNBP2NL), and two neuroendocrine-related genes, SET domain containing 6 (SETD6) and calcium channel, voltage-dependent, beta 2 subunit (CACNB2
Associations between schizophrenia and genes that encode voltage-gated calcium channel subunits, including CACNA1C, CACNB2
, and CACNA11, also were observed.
This pathway includes the genes CACNA1C and CACNB2
, whose proteins touch each other as part of an important process in nerve cells.
Variation in another calcium channel gene, called CACNB2
, was also linked to the five disorders.
(1) The specific genetic link across those 5 disorders, identified by a commonly used genetic method called a genome-wide association study (GWAS), was a set of 4 risk loci on chromosomes 3 and 10, as well as a single nucleotide polymorphism (SNP) of 2 genes called calcium channel [alpha]-1C (CACNA1C) and CACNB2
, both of which are involved in neuronal calcium channel signaling.