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 M
AU - Leach, Robin J.
AU - Flores, Deborah
AU - Jerez, Alvaro
AU - Raventós, Henriette
AU - Ontiveros, Alfonso
AU - Nicolini, Humberto
AU - Escamilla, Michael
N1 - Publisher Copyright:
© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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.
KW - Aryl Hydrocarbon Receptor Nuclear Translocator-Like
KW - Bipolar disorder
KW - Casein Kinase 1 Epsilon
KW - Circadian
KW - Family-based association test
KW - Latino
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U2 - 10.1016/j.jad.2015.07.014
DO - 10.1016/j.jad.2015.07.014
M3 - Article
C2 - 26283580
AN - SCOPUS:84939126602
SN - 0165-0327
VL - 186
SP - 367
EP - 375
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -