Supplementary Material for: Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1

Background: Bipolar disorder (BPD) is a common and
severe mental disorder. The involvement of genetic factors in the
pathophysiology of BPD is well known. In the present study, we tested
the association of several single-nucleotide polymorphisms (SNPs) within
3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These
genes are involved in monoamine-related pathways, as well as in dendrite
development, neuronal survival, synaptic plasticity, and
memory/learning. Methods: One hundred and thirty-two
subjects diagnosed with BPD and 326 healthy controls of Korean ancestry
were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1.
Distribution of alleles and block of haplotypes within each gene were
compared in cases and controls. Interactions between variants in
different loci were also tested. Results: Significant
differences in the distribution of alleles between the cases and
controls were detected for rs1016388 within CACNA1C, rs1514250,
rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and
rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement
of variations within these genes in BPD. Finally, exploratory epistatic
analyses demonstrated potential interactive effects, especially
regarding variations in CACNA1C and CHRNA7. Limitations: Limited sample size and risk of false-positive findings. Discussion:
Our data suggest a possible role of these 3 genes in BPD. Alterations
of 1 or more common brain pathways (e.g., neurodevelopment and
neuroplasticity, calcium signaling) may explain the obtained results.