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

A family-based association study

Suzanne Gonzalez, Chun Xu, Mercedes Ramirez, Juan Zavala, Regina Armas, Salvador A. Contreras, Javier Contreras, Albana M Dassori, Robin J Leach, Deborah Flores, Alvaro Jerez, Henriette Raventós, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)206-214
Number of pages9
JournalBipolar Disorders
Volume15
Issue number2
DOIs
StatePublished - Mar 2013

Fingerprint

Calcium Channels
Bipolar Disorder
Hispanic Americans
Haplotypes
Single Nucleotide Polymorphism
Genes
Genome-Wide Association Study
Population
Guatemala
Costa Rica
L-Type Calcium Channels
Pedigree
Mexico
Software
Odds Ratio
Genotype

Keywords

  • Bipolar disorder
  • Calcium channels
  • Genetic association studies
  • Haplotypes
  • Hispanic Americans
  • L-type
  • Pedigree
  • Polymorphism
  • Single nucleotide

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos : A family-based association study. / Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A.; Contreras, Javier; Dassori, Albana M; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael.

In: Bipolar Disorders, Vol. 15, No. 2, 03.2013, p. 206-214.

Research output: Contribution to journalArticle

Gonzalez, S, Xu, C, Ramirez, M, Zavala, J, Armas, R, Contreras, SA, Contreras, J, Dassori, AM, Leach, RJ, Flores, D, Jerez, A, Raventós, H, Ontiveros, A, Nicolini, H & Escamilla, M 2013, 'Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: A family-based association study', Bipolar Disorders, vol. 15, no. 2, pp. 206-214. https://doi.org/10.1111/bdi.12041
Gonzalez, Suzanne ; Xu, Chun ; Ramirez, Mercedes ; Zavala, Juan ; Armas, Regina ; Contreras, Salvador A. ; Contreras, Javier ; Dassori, Albana M ; Leach, Robin J ; Flores, Deborah ; Jerez, Alvaro ; Raventós, Henriette ; Ontiveros, Alfonso ; Nicolini, Humberto ; Escamilla, Michael. / Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos : A family-based association study. In: Bipolar Disorders. 2013 ; Vol. 15, No. 2. pp. 206-214.
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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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author = "Suzanne Gonzalez and Chun Xu and Mercedes Ramirez and Juan Zavala and Regina Armas and Contreras, {Salvador A.} and Javier Contreras and Dassori, {Albana M} and Leach, {Robin J} and Deborah Flores and Alvaro Jerez and Henriette Ravent{\'o}s and Alfonso Ontiveros and Humberto Nicolini and Michael Escamilla",
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T1 - Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos

T2 - A family-based association study

AU - Gonzalez, Suzanne

AU - Xu, Chun

AU - Ramirez, Mercedes

AU - Zavala, Juan

AU - Armas, Regina

AU - Contreras, Salvador A.

AU - Contreras, Javier

AU - Dassori, Albana M

AU - Leach, Robin J

AU - Flores, Deborah

AU - Jerez, Alvaro

AU - Raventós, Henriette

AU - Ontiveros, Alfonso

AU - Nicolini, Humberto

AU - Escamilla, Michael

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N2 - 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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