Genetic Variation in CACNA1C Affects Brain Circuitries Related to Mental Illness

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Abstract
Several research groups have performed independent genome-wide association studies1-3 of bipolar disorder, with little agreement about the most associated loci. However, a comparison of the Wellcome Trust Case Control Consortium and STEP-UCL studies identified CACNA1C (α-1C subunit of the L-type voltage-gated calcium channel) as showing the strongest consistent signal.3 The most risk-associated single-nucleotide polymorphism (SNP) in this region (rs1006737) across the 2 studies showed association in a separate data set, the so-called ED-DUB-STEP2, as well as in a combined analysis of the 2 data sets (rs1006737, P = 7.0 × 10−8),4 providing further evidence that CACNA1C is a credible susceptibility locus for bipolar disorder.