The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders

Alexandre Bureau, Jean Martin Beaulieu, Thomas Paccalet, Yvon C. Chagnon, Michel Maziade

Research output: Contribution to journalArticle

Abstract

Background Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. Methods Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. Results In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. Limitations Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. Conclusions We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.

Original languageEnglish (US)
Pages (from-to)172-177
Number of pages6
JournalJournal of Affective Disorders
Volume213
DOIs
StatePublished - Apr 15 2017
Externally publishedYes

Fingerprint

Mood Disorders
Bipolar Disorder
Genotype
Depression
Schizophrenia
Symptom Assessment
Quebec
Age of Onset
Diagnostic and Statistical Manual of Mental Disorders
Sample Size
Healthy Volunteers
Logistic Models
History
Alleles

Keywords

  • Age of onset
  • Bipolar disorder
  • Epistasis, genetic
  • Fragile X autosomal homolog 1, Glycogen Synthase Kinase 3
  • Lithium

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders. / Bureau, Alexandre; Beaulieu, Jean Martin; Paccalet, Thomas; Chagnon, Yvon C.; Maziade, Michel.

In: Journal of Affective Disorders, Vol. 213, 15.04.2017, p. 172-177.

Research output: Contribution to journalArticle

Bureau, Alexandre ; Beaulieu, Jean Martin ; Paccalet, Thomas ; Chagnon, Yvon C. ; Maziade, Michel. / The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders. In: Journal of Affective Disorders. 2017 ; Vol. 213. pp. 172-177.
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abstract = "Background Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. Methods Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. Results In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11{\%} of mania variance and 5{\%} of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. Limitations Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. Conclusions We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.",
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AU - Bureau, Alexandre

AU - Beaulieu, Jean Martin

AU - Paccalet, Thomas

AU - Chagnon, Yvon C.

AU - Maziade, Michel

PY - 2017/4/15

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N2 - Background Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. Methods Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. Results In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. Limitations Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. Conclusions We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.

AB - Background Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. Methods Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. Results In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. Limitations Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. Conclusions We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.

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KW - Fragile X autosomal homolog 1, Glycogen Synthase Kinase 3

KW - Lithium

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