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CRY1 Variations Impacts on the Depressive Relapse Rate in a Sample of Bipolar Patients.

Drago A, Monti B, De Ronchi D, Serretti A - Psychiatry Investig (2015)

Bottom Line: A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects.No other significant associations were reported.Independent confirmation analyses are mandatory.

View Article: PubMed Central - PubMed

Affiliation: I.R.C.C.S. "San Giovanni di Dio", Fatebenefratelli, Brescia, Italy.

ABSTRACT

Objective: A relevant part of the social and personal burden caused by Bipolar Disorder (BD) is related to depressive phases. Authors investigated the genetic impact of a set of variations located in CRY1, a gene involved in the control of the circadian rhythms, towards depressive episodes in a sample of bipolar patients from the STEP-BD sample. As a secondary analysis, CYR1 variations were analyzed as predictors of sleep disruption.

Methods: 654 bipolar patients were included in the analysis. Data were available genome-wide. The part of the genome coding for the CRY1 was imputed and pruned according to standards in the field. 7 SNPs were available for the analysis. A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects.

Results: Intronic rs10861688 was associated with the number of depressive events corrected for the times patients were assessed during the period of observation. In particular, AA subjects (n=21) had 4.46±3.15 events, AG (n=141) had 3.08±3.17 and GG (n=342) 2.65±2.97 (p=0.0048, beta=-0.22). No other significant associations were reported.

Conclusion: We bring further evidence that genes involved in the regulation of circadian rhythms may be relevant to depressive bipolar phases. Independent confirmation analyses are mandatory.

No MeSH data available.


Related in: MedlinePlus

Refer to the attached file. DARS2: aspartyl-tRNA synthetase 2, NPAS2: neuronal PAS domain protein 2, PER2: period circadian clock 2, CRY2: cryptochrome circadian clock 2, ARNTL: aryl hydrocarbon receptor nuclear translocator-like, PER1: period circadian clock 1, CLOCK: clock circadian regulator, PER3: period circadian clock 3, KDM5B: lysine (K)-specific demethylase 5B, CEP70: centrosomal protein 70 kDa, CSNK1E: casein kinase 1, epsilon, TIMELESS: timeless circadian clock, ADO: 2-aminoethanethiol (cysteamine) dioxygenase, HERC5: HECT and RLD domain containing E3 ubiquitin protein ligase 5, SMNDC1: survival motor neuron domain containing 1, FBXL3: F-box and leucine-rich repeat protein 3, ARFGAP3: ADP-ribosylation factor GTPase activating protein 3, CSNK1A1: casein kinase 1, alpha 1, MAP4K5: mitogen-activated protein kinase kinase kinase kinase 5, RBBP4: retinoblastoma binding protein 4.
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Figure 1: Refer to the attached file. DARS2: aspartyl-tRNA synthetase 2, NPAS2: neuronal PAS domain protein 2, PER2: period circadian clock 2, CRY2: cryptochrome circadian clock 2, ARNTL: aryl hydrocarbon receptor nuclear translocator-like, PER1: period circadian clock 1, CLOCK: clock circadian regulator, PER3: period circadian clock 3, KDM5B: lysine (K)-specific demethylase 5B, CEP70: centrosomal protein 70 kDa, CSNK1E: casein kinase 1, epsilon, TIMELESS: timeless circadian clock, ADO: 2-aminoethanethiol (cysteamine) dioxygenase, HERC5: HECT and RLD domain containing E3 ubiquitin protein ligase 5, SMNDC1: survival motor neuron domain containing 1, FBXL3: F-box and leucine-rich repeat protein 3, ARFGAP3: ADP-ribosylation factor GTPase activating protein 3, CSNK1A1: casein kinase 1, alpha 1, MAP4K5: mitogen-activated protein kinase kinase kinase kinase 5, RBBP4: retinoblastoma binding protein 4.

Mentions: CRY1 was the candidate gene for the analysis. Variations located in its genomic frame were imputed and pruned, please refer to the following paragraph. Moreover, the entire CYR1 molecular pathway was investigated as a secondary analysis. Candidates were selected according to the Cytoskape (http://www.cytoscape.org/) analysis of the CRY1 molecular pathway (Figure 1).


CRY1 Variations Impacts on the Depressive Relapse Rate in a Sample of Bipolar Patients.

Drago A, Monti B, De Ronchi D, Serretti A - Psychiatry Investig (2015)

Refer to the attached file. DARS2: aspartyl-tRNA synthetase 2, NPAS2: neuronal PAS domain protein 2, PER2: period circadian clock 2, CRY2: cryptochrome circadian clock 2, ARNTL: aryl hydrocarbon receptor nuclear translocator-like, PER1: period circadian clock 1, CLOCK: clock circadian regulator, PER3: period circadian clock 3, KDM5B: lysine (K)-specific demethylase 5B, CEP70: centrosomal protein 70 kDa, CSNK1E: casein kinase 1, epsilon, TIMELESS: timeless circadian clock, ADO: 2-aminoethanethiol (cysteamine) dioxygenase, HERC5: HECT and RLD domain containing E3 ubiquitin protein ligase 5, SMNDC1: survival motor neuron domain containing 1, FBXL3: F-box and leucine-rich repeat protein 3, ARFGAP3: ADP-ribosylation factor GTPase activating protein 3, CSNK1A1: casein kinase 1, alpha 1, MAP4K5: mitogen-activated protein kinase kinase kinase kinase 5, RBBP4: retinoblastoma binding protein 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310909&req=5

Figure 1: Refer to the attached file. DARS2: aspartyl-tRNA synthetase 2, NPAS2: neuronal PAS domain protein 2, PER2: period circadian clock 2, CRY2: cryptochrome circadian clock 2, ARNTL: aryl hydrocarbon receptor nuclear translocator-like, PER1: period circadian clock 1, CLOCK: clock circadian regulator, PER3: period circadian clock 3, KDM5B: lysine (K)-specific demethylase 5B, CEP70: centrosomal protein 70 kDa, CSNK1E: casein kinase 1, epsilon, TIMELESS: timeless circadian clock, ADO: 2-aminoethanethiol (cysteamine) dioxygenase, HERC5: HECT and RLD domain containing E3 ubiquitin protein ligase 5, SMNDC1: survival motor neuron domain containing 1, FBXL3: F-box and leucine-rich repeat protein 3, ARFGAP3: ADP-ribosylation factor GTPase activating protein 3, CSNK1A1: casein kinase 1, alpha 1, MAP4K5: mitogen-activated protein kinase kinase kinase kinase 5, RBBP4: retinoblastoma binding protein 4.
Mentions: CRY1 was the candidate gene for the analysis. Variations located in its genomic frame were imputed and pruned, please refer to the following paragraph. Moreover, the entire CYR1 molecular pathway was investigated as a secondary analysis. Candidates were selected according to the Cytoskape (http://www.cytoscape.org/) analysis of the CRY1 molecular pathway (Figure 1).

Bottom Line: A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects.No other significant associations were reported.Independent confirmation analyses are mandatory.

View Article: PubMed Central - PubMed

Affiliation: I.R.C.C.S. "San Giovanni di Dio", Fatebenefratelli, Brescia, Italy.

ABSTRACT

Objective: A relevant part of the social and personal burden caused by Bipolar Disorder (BD) is related to depressive phases. Authors investigated the genetic impact of a set of variations located in CRY1, a gene involved in the control of the circadian rhythms, towards depressive episodes in a sample of bipolar patients from the STEP-BD sample. As a secondary analysis, CYR1 variations were analyzed as predictors of sleep disruption.

Methods: 654 bipolar patients were included in the analysis. Data were available genome-wide. The part of the genome coding for the CRY1 was imputed and pruned according to standards in the field. 7 SNPs were available for the analysis. A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects.

Results: Intronic rs10861688 was associated with the number of depressive events corrected for the times patients were assessed during the period of observation. In particular, AA subjects (n=21) had 4.46±3.15 events, AG (n=141) had 3.08±3.17 and GG (n=342) 2.65±2.97 (p=0.0048, beta=-0.22). No other significant associations were reported.

Conclusion: We bring further evidence that genes involved in the regulation of circadian rhythms may be relevant to depressive bipolar phases. Independent confirmation analyses are mandatory.

No MeSH data available.


Related in: MedlinePlus