Shimasaki Ayu, Kondo Kenji, Saito Takeo, Esaki Kosei, Otsuka Yasuyo, Mano Keiko, Ikeda Masashi, Iwata Nakao
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Division of Nursing, Fujita Health University Hospital, Toyoake, Aichi, Japan.
PLoS One. 2014 Dec 17;9(12):e115135. doi: 10.1371/journal.pone.0115135. eCollection 2014.
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.
全基因组关联研究（GWASs）已经确定了一些精神分裂症（SCZ）和双相情感障碍（BD）的易感基因。然而，由于重度抑郁症（MDD）的病因受环境因素影响更大，因此确定MDD的风险基因一直未成功；因此，基因-环境（G×E）相互作用很重要，例如与应激性生活事件（SLEs）的相互作用。我们评估了针对抑郁症状的基因的G×E相互作用和主要效应。采用病例对照设计，根据贝克抑郁量表（BDI；“抑郁”和“对照”组通过BDI测试中10分的得分进行分类）、SLEs和人格对922名医院工作人员的抑郁症状进行评估。基于先前对MDD、SCZ和BD的GWAS以及候选基因（SLC6A4、BDNF、DBH和FKBP5）研究，共选择了63个基因变异。逻辑回归分析显示，rs4523957处存在边缘显著的相互作用（基因变异×SLE）与抑郁相关（P未校正 = 0.0034），并且从BD的GWAS证据中鉴定出的单核苷酸多态性（rs7296288，位于12q13.1的DHH下游）与抑郁作为主要效应显著相关（P未校正 = 9.4×10⁻⁴，P校正 = 0.0424）。我们还发现，如先前报道的那样，SLEs对抑郁的影响更大（优势比约为3）。这些结果表明，DHH在抑郁症病因中可能起作用；然而，来自MDD或SCZ的GWAS证据或候选基因的变异与SLEs对抑郁的相互作用未显示出显著关联或最小效应。
