Key result
The schizophrenia-associated risk allele (A) of rs1006737 is correlated with decreased expression of CACNA1C transcripts in the superior temporal gyrus.
p-value: p=1.14 x 10^-3
The study elucidates the pathogenic relevance of the CACNA1C risk locus for schizophrenia and bipolar disorder by demonstrating allele-dependent regulatory functions and chromatin interactions.
May link schizophrenia genetics to cardiac calcium channel function; leaves open effects on cardiac electrophysiology or drug responses.
Calcium channel subunits, including CACNA1C, have been associated with multiple psychiatric disorders. Specifically, genome wide association studies (GWAS) have repeatedly identified the single nucleotide polymorphism (SNP) rs1006737 in intron 3 of CACNA1C to be strongly associated with schizophrenia and bipolar disorder. Here, we show that rs1006737 marks a quantitative trait locus for CACNA1C transcript levels. We test 16 SNPs in high linkage disequilibrium with rs1007637 and find one, rs4765905, consistently showing allele-dependent regulatory function in reporter assays. We find allele-specific protein binding for 13 SNPs including rs4765905. Using protein microarrays, we identify several proteins binding ≥3 SNPs, but not control sequences, suggesting possible functional interactions and combinatorial haplotype effects. Finally, using circular chromatin conformation capture, we show interaction of the disease-associated region including the 16 SNPs with the CACNA1C promoter and other potential regulatory regions. Our results elucidate the pathogenic relevance of one of the best-supported risk loci for schizophrenia and bipolar disorder.
No takes yet. Share an insight, caveat, or question.
Eckart et al. (2016) studied Schizophrenia and Bipolar Disorder (n=272). rs1006737 risk allele (A) vs. Non-risk allele was evaluated on CACNA1C transcript levels in the superior temporal gyrus (p=1.14 x 10^-3). The schizophrenia-associated risk allele (A) of rs1006737 is correlated with decreased expression of CACNA1C transcripts in the superior temporal gyrus.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: