CACNA1C hypermethylation is associated with bipolar disorder.

9 , 10 , 11 A large GWAS of SZ (including 36 989 cases and 113 075 controls) performed by the PGC identified a highly significant association of rs2007044 in intron 3 of CACNA1C with SZ ( P =2.63 × 10 −17 ). 12 A recent meta analysis further supported association of CACNA1C with SZ, with rs4765905 positioned in intron 3 as the best finding ( P =5.14 × 10 −17 ). 13 It is clear, that although arrays, imputation methods and the best-associated SNPs may vary between studies, the association with both BP and SZ robustly originates from a relatively narrow set of SNPs positioned in the large intron 3 of CACNA1C .

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This GWAS showed nominally significant association of rs1006737 located in intron 3 of CACNA1C ( P =1 × 10 −4 ) with BD. 5 Subsequently, a larger GWAS with 4387 BD cases and 6209 controls, including overlapping samples from the first study, further supported the association of rs1006737, now reaching borderline genome-wide significance

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