The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population.
The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population.
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DOI：
10.1371/journal.pone.0160823
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sasaki T
中科院分区：
文献类型：
--
作者：
Otowa T;Kawamura Y;Tsutsumi A;Kawakami N;Kan C;Shimada T;Umekage T;Kasai K;Tokunaga K;Sasaki T
压力事件已被确定为抑郁症的风险因素。虽然已经探索了有限数量的候选基因中的基因-环境（G × E）相互作用，但尚未报道全基因组搜索。本研究的目的是确定影响压力事件与抑郁症关联的基因。因此，我们在日本人群中进行了全基因组G × E相互作用分析。使用Affytron全基因组人类阵列6.0对320名受试者进行全基因组筛选。采用社会再适应量表（SRRS）评估应激性生活事件，采用流行病学研究中心抑郁量表（CES-D）自评问卷评估抑郁症状。单核苷酸多态性（SNPs）和压力事件之间的相互作用的p值计算使用线性回归模型调整性别和年龄。在基因型数据的质量控制之后，对常染色体上总共534，848个SNP进行了进一步分析。虽然没有一个超过全基因组显著性水平，但发现SRRS和rs 10510057之间的相互作用与抑郁症之间存在边缘显著性关联（p = 4.5 × 10−8）。SNP位于10 q26上靠近G蛋白信号调节子10（RGS 10），其编码参与应激反应的调节分子。当我们在一个独立样本（n = 439）中研究抑郁（K6量表）和工作相关压力之间类似的G × E相互作用时，观察到G × E对抑郁的显著影响（p = 0.015）。我们的研究结果表明，rs 10510057与压力源相互作用，可能与抑郁风险有关。将G × E互作引入GWAS有助于发现传统GWAS可能遗漏的易感位点。
Stressful events have been identified as a risk factor for depression. Although gene–environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10−8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS.