Identification of circadian gene variants in bipolar disorder in Latino populations.
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 (473BP 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.


CONCLUSIONS
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.
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA. Electronic address: Robert99.Gonzalez@ttuhsc.edu.
Robert
R
Gonzalez
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Suzanne
S
Gonzalez
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Erika
E
Villa
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Mercedes
M
Ramirez
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Juan
J
Zavala
Langley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, CA, USA.
Regina
R
Armas
Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica.
Javier
J
Contreras
Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; South Texas Veterans Health Care System, San Antonio, TX, USA.
Albana
A
Dassori
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Robin J
RJ
Leach
Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, CA, USA.
Deborah
D
Flores
Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva, Guatemala, Guatemala.
Alvaro
A
Jerez
Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica.
Henriette
H
Raventós
Instituto de Información e Investigación en Salud Mental AC, Monterrey, Nuevo Leon, Mexico.
Alfonso
A
Ontiveros
Grupo de Estudios Médicos y Familiares Carracci, S.C., México, D.F., Mexico.
Humberto
H
Nicolini
Department of Psychiatry and Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Michael
M
Escamilla
D056930:ARNTL Transcription Factors / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics*; D048149:Casein Kinase 1 epsilon / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D056926:CLOCK Proteins; C538943:CLOCK protein, human; D048149:Casein Kinase 1 epsilon
Aryl Hydrocarbon Receptor Nuclear Translocator-Like; Bipolar disorder; Casein Kinase 1 Epsilon; Circadian; Family-based association test; Latino