Association between rs2799573 and psychiatric disorders was shown in a 2013 study by the Cross-Disorder Group of the Psychiatric Genomics Consortium [PMID 23453885]. In this study, genome-wide SNP data consisting of 1,250,922 autosomal SNPs were analyzed to identify genetic variants associated with autism spectrum disorder, ADHD, bipolar disorder, major depressive disorder, and schizophrenia. 33,332 cases and 27,888 controls included both unrelated and family-based samples (trios). A multinomial logistic regression procedure was used to identify the best-fitting model of relations between genotype and phenotype.
This SNP, on chromosome 10 in an intron of CACNB2, was one of four genome-wide significant signals associated with the five psychiatric disorders (p = 4.29 x 10-8). The risk allele T exhibited allele frequency of 0.715 in controls. CACNB2 encodes a voltage-gated calcium-channel subunit that interacts with other calcium-channel subunits to facilitate their function and increase peak calcium current. Although CACNB2 had not been previously identified as a risk gene for schizophrenia and bipolar disorder, its interactor CACNA1C, was known to be a susceptibility gene for bipolar disorder [PMID 21926972], schizophrenia, and major depressive disorder [PMID 19621016]. Effects of CACNA1C variants on emotion processing circuitry, attention, and memory were demonstrated in fMRI studies [PMID 20819988][PMID 21078228]. Consistent with this, one of the four significant signals from the 2013 study lies within an intron of CACNA1C. Other peaks identified in this study were rs2535629 and rs11191454.
In addition, a variant within CACNB2 52 kb away from rs2799573 was one of the most significant signals in an independent GWAS of bipolar disorder in Han Chinese[PMID 20386566]. All samples analyzed in the Cross-Disorder Group of the Psychiatric Genomics Consortium study were of European ancestry.