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 (G × E) interactions are important, such as interplay with stressful life events (SLEs). We assessed the G×E 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 × SLE) at rs4523957 (P uncorrected = 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 (P uncorrected = 9.4 × 10(-4), P corrected = 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.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Ayu
authors.initials: A
authors.lastname: Shimasaki
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Esaki
authors.affiliation: Division of Nursing, Fujita Health University Hospital, Toyoake, Aichi, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Otsuka
authors.affiliation: Division of Nursing, Fujita Health University Hospital, Toyoake, Aichi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Mano
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers