Identification of circadian gene variants in bipolar disorder in Latino populations

Robert Gonzalez, Suzanne Gonzalez, Erika Villa, Mercedes Ramirez, Juan Zavala, Regina Armas, Javier Contreras, Albana Dassori, Robin J. Leach, Deborah Flores, Alvaro Jerez, Henriette Raventós, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness. Methods A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees. 884 individuals from 207 pedigrees (473 BP phenotype and 411 unaffected family members) were genotyped. Family based single marker association testing was performed. Ancestral haplotypes (SNPs found to be in strong LD defined using confidence intervals) were also tested for association with BD. Results Multiple suggestive associations between circadian gene SNPs and BD were noted. These included CSNK1E (rs1534891, p=0.00689), ARNTL (rs3789327, p=0.021172), CSNK1D (rs4510078, p=0.022801), CLOCK (rs17777927, p=0.031664). Individually, none of the SNPs were significantly associated with BD after correction for multiple testing. However, a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with BD. Limitations Larger samples are required to confirm these findings and assess the relationship between circadian gene SNPs and BD in Latinos. Conclusions The results suggest that ARNTL and CSKN1E variants may be associated with BD. Further studies are warranted to assess the relationships between these genes and BD in Latino populations.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalJournal of Affective Disorders
Volume186
DOIs
StatePublished - Aug 17 2015

Fingerprint

Bipolar Disorder
Hispanic Americans
Single Nucleotide Polymorphism
Population
Genes
Haplotypes
Pedigree
Gene Components
Periodicity
Confidence Intervals
Phenotype

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Gonzalez, Robert ; Gonzalez, Suzanne ; Villa, Erika ; Ramirez, Mercedes ; Zavala, Juan ; Armas, Regina ; Contreras, Javier ; Dassori, Albana ; Leach, Robin J. ; Flores, Deborah ; Jerez, Alvaro ; Raventós, Henriette ; Ontiveros, Alfonso ; Nicolini, Humberto ; Escamilla, Michael. / Identification of circadian gene variants in bipolar disorder in Latino populations. In: Journal of Affective Disorders. 2015 ; Vol. 186. pp. 367-375.
@article{2fe1b5a4f814429ebf7ca79fb43e8acb,
title = "Identification of circadian gene variants in bipolar disorder in Latino populations",
abstract = "Background Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness. Methods A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees. 884 individuals from 207 pedigrees (473 BP phenotype and 411 unaffected family members) were genotyped. Family based single marker association testing was performed. Ancestral haplotypes (SNPs found to be in strong LD defined using confidence intervals) were also tested for association with BD. Results Multiple suggestive associations between circadian gene SNPs and BD were noted. These included CSNK1E (rs1534891, p=0.00689), ARNTL (rs3789327, p=0.021172), CSNK1D (rs4510078, p=0.022801), CLOCK (rs17777927, p=0.031664). Individually, none of the SNPs were significantly associated with BD after correction for multiple testing. However, a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with BD. Limitations Larger samples are required to confirm these findings and assess the relationship between circadian gene SNPs and BD in Latinos. Conclusions The results suggest that ARNTL and CSKN1E variants may be associated with BD. Further studies are warranted to assess the relationships between these genes and BD in Latino populations.",
author = "Robert Gonzalez and Suzanne Gonzalez and Erika Villa and Mercedes Ramirez and Juan Zavala and Regina Armas and Javier Contreras and Albana Dassori and Leach, {Robin J.} and Deborah Flores and Alvaro Jerez and Henriette Ravent{\'o}s and Alfonso Ontiveros and Humberto Nicolini and Michael Escamilla",
year = "2015",
month = "8",
day = "17",
doi = "10.1016/j.jad.2015.07.014",
language = "English (US)",
volume = "186",
pages = "367--375",
journal = "Journal of Affective Disorders",
issn = "0165-0327",
publisher = "Elsevier",

}

Gonzalez, R, Gonzalez, S, Villa, E, Ramirez, M, Zavala, J, Armas, R, Contreras, J, Dassori, A, Leach, RJ, Flores, D, Jerez, A, Raventós, H, Ontiveros, A, Nicolini, H & Escamilla, M 2015, 'Identification of circadian gene variants in bipolar disorder in Latino populations', Journal of Affective Disorders, vol. 186, pp. 367-375. https://doi.org/10.1016/j.jad.2015.07.014

Identification of circadian gene variants in bipolar disorder in Latino populations. / Gonzalez, Robert; Gonzalez, Suzanne; Villa, Erika; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Javier; Dassori, Albana; Leach, Robin J.; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael.

In: Journal of Affective Disorders, Vol. 186, 17.08.2015, p. 367-375.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of circadian gene variants in bipolar disorder in Latino populations

AU - Gonzalez, Robert

AU - Gonzalez, Suzanne

AU - Villa, Erika

AU - Ramirez, Mercedes

AU - Zavala, Juan

AU - Armas, Regina

AU - Contreras, Javier

AU - Dassori, Albana

AU - Leach, Robin J.

AU - Flores, Deborah

AU - Jerez, Alvaro

AU - Raventós, Henriette

AU - Ontiveros, Alfonso

AU - Nicolini, Humberto

AU - Escamilla, Michael

PY - 2015/8/17

Y1 - 2015/8/17

N2 - Background Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness. Methods A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees. 884 individuals from 207 pedigrees (473 BP phenotype and 411 unaffected family members) were genotyped. Family based single marker association testing was performed. Ancestral haplotypes (SNPs found to be in strong LD defined using confidence intervals) were also tested for association with BD. Results Multiple suggestive associations between circadian gene SNPs and BD were noted. These included CSNK1E (rs1534891, p=0.00689), ARNTL (rs3789327, p=0.021172), CSNK1D (rs4510078, p=0.022801), CLOCK (rs17777927, p=0.031664). Individually, none of the SNPs were significantly associated with BD after correction for multiple testing. However, a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with BD. Limitations Larger samples are required to confirm these findings and assess the relationship between circadian gene SNPs and BD in Latinos. Conclusions The results suggest that ARNTL and CSKN1E variants may be associated with BD. Further studies are warranted to assess the relationships between these genes and BD in Latino populations.

AB - Background Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness. Methods A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees. 884 individuals from 207 pedigrees (473 BP phenotype and 411 unaffected family members) were genotyped. Family based single marker association testing was performed. Ancestral haplotypes (SNPs found to be in strong LD defined using confidence intervals) were also tested for association with BD. Results Multiple suggestive associations between circadian gene SNPs and BD were noted. These included CSNK1E (rs1534891, p=0.00689), ARNTL (rs3789327, p=0.021172), CSNK1D (rs4510078, p=0.022801), CLOCK (rs17777927, p=0.031664). Individually, none of the SNPs were significantly associated with BD after correction for multiple testing. However, a 4-locus CSNK1E haplotype encompassing the rs1534891 SNP (Z-score=2.685, permuted p=0.0076) and a 3-locus haplotype in ARNTL (Z-score=3.269, permuted p=0.0011) showed a significant association with BD. Limitations Larger samples are required to confirm these findings and assess the relationship between circadian gene SNPs and BD in Latinos. Conclusions The results suggest that ARNTL and CSKN1E variants may be associated with BD. Further studies are warranted to assess the relationships between these genes and BD in Latino populations.

UR - http://www.scopus.com/inward/record.url?scp=84939126602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939126602&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2015.07.014

DO - 10.1016/j.jad.2015.07.014

M3 - Article

VL - 186

SP - 367

EP - 375

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

ER -