PER2 variantion is associated with depression vulnerability.
The circadian clock is driven by transcription-translation feedback loops and regulates rhythms that approximate the 24-hr day-night cycle or light-dark transitions. Disruptions of the circadian rhythms are common in depressed patients, expressed for example as sleep disturbances. Genetic variations in core circadian genes may in part explain these abnormalities. To investigate whether genetic variation in core circadian genes associates with vulnerability to depression, we genotyped 18 genes in a Swedish population based sample. Genetic variations indicative of association with depression, or with winter depression in our previous study, were tested for association to depression in a second Swedish depression-control sample set. PER2 genetic variation was associated with depression vulnerability, and this genetic risk did not seem to require exposure to potential sleep disturbance factors such as negative life event or financial strain that are known to increase the risk for depression. Polymorphisms in the circadian genes NPAS2, ARNTL, and RORA were also suggested to contribute to depression vulnerability. The findings we report for PER2, ARNTL, and RORA are supported by at least two of the three sample sets. In conclusion, genetic variation in PER2 is associated with depression vulnerability a Swedish population-based sample. More studies are needed to determine if this is the case also for NPAS2, ARNTL, and RORA.
Lavebratt
Catharina
C
Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
Sjöholm
Louise K
LK
Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
Partonen
Timo
T
Department of Mental Health and Alcohol Research, National Institute of Health and Welfare, Helsinki, Finland.
Schalling
Martin
M
Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
Forsell
Yvonne
Y
Department of Public Health Science, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden.
D000328:Adult; D002940:Circadian Rhythm / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D013548:Sweden; D013997:Time Factors
C421902:PER2 protein, human; D056950:Period Circadian Proteins