A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events

Ayu Shimasaki, Kenji Kondo, Takeo Saito, Kosei Esaki, Yasuyo Otsuka, Keiko Mano, Masashi Ikeda, Nakao Iwata

Research output: Contribution to journalArticle

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Abstract

Genome-wide association studies (GWASs) have identified a number of susceptibility genes for schizophrenia (SCZ) and bipolar disorder (BD). However, the identification of risk genes for major depressive disorder (MDD) has been unsuccessful because the etiology of MDD is more influenced by environmental factors; thus, gene-environment (GxE) interactions are important, such as interplay with stressful life events (SLEs). We assessed the GxE interactions and main effects of genes targeting depressive symptoms. Using a case-control design, 922 hospital staff members were evaluated for depressive symptoms according to Beck Depressive Inventory (BDI; "depression" and "control" groups were classified by scores of 10 in the BDI test), SLEs, and personality. A total of sixty-three genetic variants were selected on the basis of previous GWASs of MDD, SCZ, and BD as well as candidate-gene (SLC6A4, BDNF, DBH, and FKBP5) studies. Logistic regression analysis revealed a marginally significant interaction (genetic variant x SLE) at rs4523957 (Puncorrected=0.0034) with depression and a significant association of single nucleotide polymorphism identified from evidence of BD GWAS (rs7296288, downstream of DHH at 12q13.1) with depression as the main effect (Puncorrected=9.461024, Pcorrected=0.0424). We also found that SLEs had a larger impact on depression (odds ratio∼3), as reported previously. These results suggest that DHH plays a possible role in depression etiology; however, variants from MDD or SCZ GWAS evidence or candidate genes showed no significant associations or minimal effects of interactions with SLEs on depression.

Original languageEnglish
Article numbere115135
JournalPloS one
Volume9
Issue number12
DOIs
Publication statusPublished - 17-12-2014

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life events
Bipolar Disorder
risk factors
Genes
Depression
Genome-Wide Association Study
Major Depressive Disorder
etiology
Schizophrenia
genes
genotype-environment interaction
gene targeting
major genes
single nucleotide polymorphism
Hospital Design and Construction
regression analysis
Gene-Environment Interaction
Gene Targeting
Brain-Derived Neurotrophic Factor
environmental factors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events",
abstract = "Genome-wide association studies (GWASs) have identified a number of susceptibility genes for schizophrenia (SCZ) and bipolar disorder (BD). However, the identification of risk genes for major depressive disorder (MDD) has been unsuccessful because the etiology of MDD is more influenced by environmental factors; thus, gene-environment (GxE) interactions are important, such as interplay with stressful life events (SLEs). We assessed the GxE interactions and main effects of genes targeting depressive symptoms. Using a case-control design, 922 hospital staff members were evaluated for depressive symptoms according to Beck Depressive Inventory (BDI; {"}depression{"} and {"}control{"} groups were classified by scores of 10 in the BDI test), SLEs, and personality. A total of sixty-three genetic variants were selected on the basis of previous GWASs of MDD, SCZ, and BD as well as candidate-gene (SLC6A4, BDNF, DBH, and FKBP5) studies. Logistic regression analysis revealed a marginally significant interaction (genetic variant x SLE) at rs4523957 (Puncorrected=0.0034) with depression and a significant association of single nucleotide polymorphism identified from evidence of BD GWAS (rs7296288, downstream of DHH at 12q13.1) with depression as the main effect (Puncorrected=9.461024, Pcorrected=0.0424). We also found that SLEs had a larger impact on depression (odds ratio∼3), as reported previously. These results suggest that DHH plays a possible role in depression etiology; however, variants from MDD or SCZ GWAS evidence or candidate genes showed no significant associations or minimal effects of interactions with SLEs on depression.",
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A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events. / Shimasaki, Ayu; Kondo, Kenji; Saito, Takeo; Esaki, Kosei; Otsuka, Yasuyo; Mano, Keiko; Ikeda, Masashi; Iwata, Nakao.

In: PloS one, Vol. 9, No. 12, e115135, 17.12.2014.

Research output: Contribution to journalArticle

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T1 - A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events

AU - Shimasaki, Ayu

AU - Kondo, Kenji

AU - Saito, Takeo

AU - Esaki, Kosei

AU - Otsuka, Yasuyo

AU - Mano, Keiko

AU - Ikeda, Masashi

AU - Iwata, Nakao

PY - 2014/12/17

Y1 - 2014/12/17

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AB - Genome-wide association studies (GWASs) have identified a number of susceptibility genes for schizophrenia (SCZ) and bipolar disorder (BD). However, the identification of risk genes for major depressive disorder (MDD) has been unsuccessful because the etiology of MDD is more influenced by environmental factors; thus, gene-environment (GxE) interactions are important, such as interplay with stressful life events (SLEs). We assessed the GxE interactions and main effects of genes targeting depressive symptoms. Using a case-control design, 922 hospital staff members were evaluated for depressive symptoms according to Beck Depressive Inventory (BDI; "depression" and "control" groups were classified by scores of 10 in the BDI test), SLEs, and personality. A total of sixty-three genetic variants were selected on the basis of previous GWASs of MDD, SCZ, and BD as well as candidate-gene (SLC6A4, BDNF, DBH, and FKBP5) studies. Logistic regression analysis revealed a marginally significant interaction (genetic variant x SLE) at rs4523957 (Puncorrected=0.0034) with depression and a significant association of single nucleotide polymorphism identified from evidence of BD GWAS (rs7296288, downstream of DHH at 12q13.1) with depression as the main effect (Puncorrected=9.461024, Pcorrected=0.0424). We also found that SLEs had a larger impact on depression (odds ratio∼3), as reported previously. These results suggest that DHH plays a possible role in depression etiology; however, variants from MDD or SCZ GWAS evidence or candidate genes showed no significant associations or minimal effects of interactions with SLEs on depression.

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