Genetic polymorphism at theCLOCK gene locus and major depression

Desan, Paul H.; Oren, Dan A.; Malison, Robert T.; Price, Lawrence H.; Rosenbaum, Jerrold F.; Smoller, Jordan W.; Charney, Dennis S.; Gelernter, Joel

doi:10.1002/1096-8628(20000612)96:3<418::aid-ajmg34>3.0.co;2-s

Cited by 89 publications

(65 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This SNP is also associated with greater insomnia and decreased need for sleep in bipolar patients, as well as greater insomnia in individuals undergoing antidepressant treatment Serretti et al, 2005). However, in patients with MDD, there appears to be no general association between the disease and this SNP (Desan et al, 2000). Since this SNP is in the 3′ flanking region, it could affect polyadenylation or RNA stability, however, these possibilities have not been tested.…”

Section: Human Genetic Studiesmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

587

386

View full text Add to dashboard Cite

For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or "resetting" the circadian clock, including total sleep deprivation and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antidepressants used to treat these disorders may derive at least some of their therapeutic efficacy by affecting the circadian clock. Recent genetic, molecular and behavioral studies implicate individual genes that make up the clock in mood regulation. As well, important functions of these genes in brain regions and neurotransmitter systems associated with mood regulation is becoming apparent. In this review, the evidence linking circadian rhythms and mood disorders, and what is known about the underlying biology of this association, is presented.

show abstract

Section: Human Genetic Studiesmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

587

386

View full text Add to dashboard Cite

show abstract

“…Genomic DNA was prepared from blood lymphocytes and genotyping for CLOCK 3111 C/T was performed as described previously (Desan et al, 2000). For the other polymorphisms, standard PCR amplifications were performed using a 50-cycle reaction with annealing temperatures of 631C forPeriod2 1244 Gly/Glu and 591C for Period3 647 Val/Gly and NPAS2 471 Leu/Ser.…”

Section: Genotypingmentioning

confidence: 99%

“…Genetic variations in genes involved in the endogenous circadian clock could have an influence on the deviations from the normal 24-h daily rhythm found in patients with affective disorder (Bunney and Bunney, 2000;Desan et al, 2000). The core of this molecular clock consists of a transcription-translation feedback loop that generates a self-sustained circadian oscillation, and can be adjusted to the environment by responding to external cues, such as new light/dark conditions (for a review see Albrecht, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…There are studies reporting that CLOCK 3111 C/T, which is located in the 3 0 flanking region of the CLOCK gene, is associated with diurnal preference (Katzenberg et al, 1998), but not major depressive disorder (Desan et al, 2000), and Period3 647 Val/Gly is suggested to be the causative polymorphism in a Period3 haplotype associated with delayed sleep phase syndrome (Ebisawa et al, 2001). There are no published association studies for Period2 1244 Gly/Glu or NPAS2 471 Leu/Ser.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Johansson

Willeit

Smedh

et al. 2002

Neuropsychopharmacol

311

194

View full text Add to dashboard Cite

Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n ¼ 177) and diurnal preference (n ¼ 92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (w 2 ¼ 9.90, Bonferroni corrected P ¼ 0.035), indicating a recessive effect of the leucine allele on disease susceptibility (w 2 ¼ 6.61, Bonferroni corrected P ¼ 0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n ¼ 92, oneway ANOVA: F ¼ 4.99, Bonferroni corrected P ¼ 0.044), with higher scores found in individuals with at least one glycine allele (t ¼ 3.1, Bonferroni corrected P ¼ 0.013). A second, population-based sample of individuals selected for high (n ¼ 127) or low (n ¼ 98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n ¼ 177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

show abstract

“…Another polymorphism reported in the literature, 3092T/C (also known as 3111T/C) was reportedly associated with the diurnal preference of evening type in Caucasians (Katzberg et al 1998), but the association was not replicated (Robilliard et al 2002). There was also no association in a study of the SNP with major depression (Desan et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Identification of human Clock gene variants by denaturing high-performance liquid chromatography

Chen

Tan

2004

J Hum Genet

View full text Add to dashboard Cite

The human Clock gene (hClock) encodes the CLOCK protein essential for the function of the circadian system. We have screened the entire coding region, including the 5¢ and 3¢ untranslated regions (UTRs) and the flanking intronic regions, of the hClock gene for sequence variations in 70 unrelated Chinese Singaporeans with denaturing high-performance liquid chromatography (dHPLC). A total of 15 sequence variations were detected, five of which were novel. All involved single base changes. There were 12 substitutions and three insertions/deletions. All except one were found in the introns or the UTRs. Frequencies of the minor allele for all 15 polymorphisms ranged from 0.7% to almost 50%. For the eight sites whose minor allele frequency was found to be at least 10%, pair-wise comparisons revealed that all except one were in almost complete linkage disequilibrium. Our identification of additional single nucleotide polymorphisms in the hClock gene would provide markers whose frequencies could be established in the selected population and used for further analysis of the phenotypic effects. Our results would also be useful for better planning in the selection of polymorphisms for future genetic association studies involving the hClock gene.

show abstract

Genetic polymorphism at theCLOCK gene locus and major depression

Cited by 89 publications

References 26 publications

Circadian genes, rhythms and the biology of mood disorders

Circadian genes, rhythms and the biology of mood disorders

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Identification of human Clock gene variants by denaturing high-performance liquid chromatography

Contact Info

Product

Resources

About