Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder
Por:
Soria, V, Martinez-Amoros, E, Escaramis, G, Valero, J, Perez-Egea, R, Garcia, C, Gutierrez-Zotes, A, Puigdemont, D, Bayes, M, Crespo, JM, Martorell, L, Vilella, E, Labad, A, Vallejo, J, Perez, V, Menchon, JM, Estivill, X, Gratacos, M, Urretavizcaya, M
Publicada:
1 may 2010
Resumen:
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 30 near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p = 0.007). 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. Neuropsychopharmacology (2010) 35, 1279-1289; doi: 10.1038/npp.2009.230; published online 13 January 2010
Filiaciones:
Soria, V:
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Martinez-Amoros, E:
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Escaramis, G:
CRG, Genes & Dis Program, CIBERESP, Barcelona 08003, Spain
Valero, J:
Univ Rovira & Virgili, Hosp Psiquiatr, Univ Inst Pere Mata, IISPV, E-43201 Reus, Spain
Perez-Egea, R:
Univ Autonoma Barcelona, CIBERSAM, Dept Psychiat, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Garcia, C:
CRG, Genom Core Facil, Barcelona 08003, Spain
CRG, Ctr Nacl Genotipado, Barcelona 08003, Spain
Gutierrez-Zotes, A:
Univ Rovira & Virgili, Hosp Psiquiatr, Univ Inst Pere Mata, IISPV, E-43201 Reus, Spain
Puigdemont, D:
Univ Autonoma Barcelona, CIBERSAM, Dept Psychiat, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Bayes, M:
CRG, Genom Core Facil, Barcelona 08003, Spain
CRG, Ctr Nacl Genotipado, Barcelona 08003, Spain
Crespo, JM:
Univ Barcelona, Dept Clin Sci, Barcelona, Spain
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Martorell, L:
Univ Rovira & Virgili, Hosp Psiquiatr, Univ Inst Pere Mata, IISPV, E-43201 Reus, Spain
Vilella, E:
Univ Rovira & Virgili, Hosp Psiquiatr, Univ Inst Pere Mata, IISPV, E-43201 Reus, Spain
Labad, A:
Univ Rovira & Virgili, Hosp Psiquiatr, Univ Inst Pere Mata, IISPV, E-43201 Reus, Spain
Vallejo, J:
Univ Barcelona, Dept Clin Sci, Barcelona, Spain
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Perez, V:
Univ Autonoma Barcelona, CIBERSAM, Dept Psychiat, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Menchon, JM:
Univ Barcelona, Dept Clin Sci, Barcelona, Spain
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Estivill, X:
Pompeu Fabra Univ, Expt & Hlth Sci Dept, Barcelona, Spain
CRG, Genes & Dis Program, CIBERESP, Barcelona 08003, Spain
Gratacos, M:
CRG, Genes & Dis Program, CIBERESP, Barcelona 08003, Spain
Urretavizcaya, M:
Univ Barcelona, Dept Clin Sci, Barcelona, Spain
Bellvitge Univ Hosp, CIBERSAM, Mood Disorders Clin & Res Unit, Dept Psychiat, Barcelona, Spain
Green Published, Bronze
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