title: Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study.
abstract: OBJECTIVE
  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.
authors: Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors: Suzanne
authors: S
authors: Gonzalez
authors: Chun
authors: C
authors: Xu
authors: Mercedes
authors: M
authors: Ramirez
authors: Juan
authors: J
authors: Zavala
authors: Regina
authors: R
authors: Armas
authors: Salvador A
authors: SA
authors: Contreras
authors: Javier
authors: J
authors: Contreras
authors: Albana
authors: A
authors: Dassori
authors: Robin J
authors: RJ
authors: Leach
authors: Deborah
authors: D
authors: Flores
authors: Alvaro
authors: A
authors: Jerez
authors: Henriette
authors: H
authors: Raventós
authors: Alfonso
authors: A
authors: Ontiveros
authors: Humberto
authors: H
authors: Nicolini
authors: Michael
authors: M
authors: Escamilla
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D003364:Costa Rica; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006166:Guatemala; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008800:Mexico; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014481:United States; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type