title: Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression.
abstract: BACKGROUND
  Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression.
  
  
  METHODS
  In silico analysis of the biological effects of allelic differences suggested the target single-nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk.
  
  
  RESULTS
  SAD was associated with variations in each of the three genes in gene-wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination.
  
  
  CONCLUSIONS
  Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.
authors: Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland. timo.partonen@ktl.fi
authors: Timo
authors: T
authors: Partonen
authors: Jens
authors: J
authors: Treutlein
authors: Asude
authors: A
authors: Alpman
authors: Josef
authors: J
authors: Frank
authors: Carolina
authors: C
authors: Johansson
authors: Martin
authors: M
authors: Depner
authors: Liviu
authors: L
authors: Aron
authors: Marcella
authors: M
authors: Rietschel
authors: Stefan
authors: S
authors: Wellek
authors: Pia
authors: P
authors: Soronen
authors: Tiina
authors: T
authors: Paunio
authors: Andreas
authors: A
authors: Koch
authors: Ping
authors: P
authors: Chen
authors: Mark
authors: M
authors: Lathrop
authors: Rolf
authors: R
authors: Adolfsson
authors: Maj-Liz
authors: ML
authors: Persson
authors: Siegfried
authors: S
authors: Kasper
authors: Martin
authors: M
authors: Schalling
authors: Leena
authors: L
authors: Peltonen
authors: Gunter
authors: G
authors: Schumann
mesh_terms: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D056950:Period Circadian Proteins; D020641:Polymorphism, Single Nucleotide; D016574:Seasonal Affective Disorder / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D014157:Transcription Factors; C538960:BMAL1 protein, human; C104264:NPAS2 protein, human; C421902:PER2 protein, human