A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression

E. Saus, V. Soria, G. Escaramís, J. M. Crespo, J. Valero, A. Gutiérrez-Zotes, L. Martorell, E. Vilella, J. M. Menchón, Xavier P. Estivill, M. Gratacòs, M. Urretavizcaya

Research output: Contribution to journalArticle

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Abstract

Recent findings suggest that glycogen synthase kinase 3β (GSK3β) may play a role in the pathophysiology and treatment of mood disorders. Various genetic studies have shown the association of GSK3β polymorphisms with different mood disorder phenotypes. We hypothesized that genetic variants in the GSK3β gene could partially underlie the susceptibility to mood disorders. We performed a genetic case-control study of 440 psychiatrically screened control subjects and 445 mood disorder patients [256 unipolar major depressive disorder (MDD) and 189 bipolar disorder (BD)]. We genotyped a set of 11 single nucleotide polymorphisms (SNPs) and determined the relative frequency of a known copy number variant (CNV) overlapping the GSK3β by quantitative real-time polymerase chain reaction (PCR). We found no evidence of association with MDD or BD diagnosis, and we further investigated the age at onset (AAO) of the disorder and severity of depressive index episode. We found that rs334555, located in intron 1 of GSK3β, was nominally associated with an earlier AAO of the disease in MDD (P = 0.001). We also identified a haplotype containing three SNPs (rs334555, rs119258668 and rs11927974) associated with AAO of the disorder (permutated P = 0.0025). We detected variability for the CNV, but we could not detect differences between patients and controls for any of the explored phenotypes. This study presents further evidence of the contribution of GSK3β to mood disorders, implicating a specific SNP and a haplotype with an earlier onset of the disorder in a group of well-characterized patients with unipolar MDD. Further replication studies in patients with the same phenotypic characteristics should confirm the results reported here.

Original languageEnglish
Pages (from-to)799-807
Number of pages9
JournalGenes, Brain and Behavior
Volume9
Issue number7
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Depressive Disorder
Haplotypes
Mood Disorders
Major Depressive Disorder
Age of Onset
Single Nucleotide Polymorphism
Bipolar Disorder
Phenotype
Introns
Case-Control Studies
Real-Time Polymerase Chain Reaction
Genes

Keywords

  • Age at onset
  • Association
  • Copy number variation
  • GSK3β
  • Mood disorders
  • Polymorphism

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Saus, E., Soria, V., Escaramís, G., Crespo, J. M., Valero, J., Gutiérrez-Zotes, A., ... Urretavizcaya, M. (2010). A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression. Genes, Brain and Behavior, 9(7), 799-807. https://doi.org/10.1111/j.1601-183X.2010.00617.x

A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression. / Saus, E.; Soria, V.; Escaramís, G.; Crespo, J. M.; Valero, J.; Gutiérrez-Zotes, A.; Martorell, L.; Vilella, E.; Menchón, J. M.; Estivill, Xavier P.; Gratacòs, M.; Urretavizcaya, M.

In: Genes, Brain and Behavior, Vol. 9, No. 7, 10.2010, p. 799-807.

Research output: Contribution to journalArticle

Saus, E, Soria, V, Escaramís, G, Crespo, JM, Valero, J, Gutiérrez-Zotes, A, Martorell, L, Vilella, E, Menchón, JM, Estivill, XP, Gratacòs, M & Urretavizcaya, M 2010, 'A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression', Genes, Brain and Behavior, vol. 9, no. 7, pp. 799-807. https://doi.org/10.1111/j.1601-183X.2010.00617.x
Saus, E. ; Soria, V. ; Escaramís, G. ; Crespo, J. M. ; Valero, J. ; Gutiérrez-Zotes, A. ; Martorell, L. ; Vilella, E. ; Menchón, J. M. ; Estivill, Xavier P. ; Gratacòs, M. ; Urretavizcaya, M. / A haplotype of glycogen synthase kinase 3β is associated with early onset of unipolar major depression. In: Genes, Brain and Behavior. 2010 ; Vol. 9, No. 7. pp. 799-807.
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