TY - JOUR
T1 - Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and clock and VIP with bipolar disorder
AU - Soria, Virginia
AU - Martínez-Amorós, Èrika
AU - Escaramís, Geòrgia
AU - Valero, Joaquín
AU - Pérez-Egea, Rosario
AU - García, Cecilia
AU - Gutiérrez-Zotes, Alfonso
AU - Puigdemont, Dolors
AU - Bayés, Mònica
AU - Crespo, José M.
AU - Martorell, Lourdes
AU - Vilella, Elisabet
AU - Labad, Antonio
AU - Vallejo, Julio
AU - Pérez, Víctor
AU - Menchón, José M.
AU - Estivill, Xavier
AU - Gratacòs, Mònica
AU - Urretavizcaya, Mikel
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3′ near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity. © 2010 Nature Publishing Group All rights reserved.
AB - Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3′ near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity. © 2010 Nature Publishing Group All rights reserved.
KW - Association
KW - Circadian rhythms
KW - Clock genes
KW - Haplotype
KW - Mood disorders
KW - Polymorphism
U2 - 10.1038/npp.2009.230
DO - 10.1038/npp.2009.230
M3 - Article
SN - 0893-133X
VL - 35
SP - 1279
EP - 1289
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 6
ER -