Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study

• Published in: Bipolar disorders 2013-03, Vol.15 (2), p.206-214
• Main Authors: Gonzalez, Suzanne, Xu, Chun, Ramirez, Mercedes, Zavala, Juan, Armas, Regina, Contreras, Salvador A, Contreras, Javier, Dassori, Albana, Leach, Robin J, Flores, Deborah, Jerez, Alvaro, Raventós, Henriette, Ontiveros, Alfonso, Nicolini, Humberto, Escamilla, Michael
• Format: Article
• Language: English
• Subjects: bipolar disorder; Bipolar Disorder - genetics; calcium channels; Calcium Channels - genetics; Costa Rica; Family Health; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Guatemala; Haplotypes; Hispanic Americans; Hispanic Americans - genetics; Humans; L-type; Male; Mexico; pedigree; polymorphism; Polymorphism, Single Nucleotide - genetics; single nucleotide; United States
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1111/bdi.12041

Objectives:  Through recent genome‐wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage‐dependent, L‐type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European‐American cohorts. We performed a family‐based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods:  This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single‐nucleotide polymorphisms (SNPs) that spanned a 602.9‐kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family‐Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results:  An eight‐locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions:  Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population.