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. CONCLUSION: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.

journal_name

Ann Med

journal_title

Annals of medicine

authors

Partonen T,Treutlein J,Alpman A,Frank J,Johansson C,Depner M,Aron L,Rietschel M,Wellek S,Soronen P,Paunio T,Koch A,Chen P,Lathrop M,Adolfsson R,Persson ML,Kasper S,Schalling M,Peltonen L,Schumann G

doi

10.1080/07853890701278795

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

229-38

issue

3

eissn

0785-3890

issn

1365-2060

pii

777658176

journal_volume

39

pub_type

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