Suggestive evidence for association between L‐type voltage‐gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family‐based association study |
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| Authors: | Suzanne Gonzalez Chun Xu Mercedes Ramirez Juan Zavala Regina Armas Salvador A Contreras Javier Contreras Albana Dassori Robin J Leach Deborah Flores Alvaro Jerez Henriette Raventós Alfonso Ontiveros Humberto Nicolini Michael Escamilla |
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| Institution: | 1. Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX;2. Langley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, CA;3. Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;4. Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica;5. South Texas Veterans Health Care System;6. Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX;7. Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, CA, USA;8. Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva, Guatemala City, Guatemala;9. Instituto de Información e Investigación en Salud Mental AC, Monterrey, Nuevo Leon;10. Grupo de Estudios Médicos y Familiares Carracci, S.C., México, D.F., México |
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| Abstract: | 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. |
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| Keywords: | bipolar disorder calcium channels genetic association studies haplotypes Hispanic Americans L‐type pedigree polymorphism single nucleotide |
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