Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.
Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.
复制标题
DOI：
10.1001/jama.2009.878
复制
发表时间：
2009-06-17
影响因子：
120.7
通讯作者：
Merikangas, Kathleen Ries
中科院分区：
文献类型：
--
作者：
Risch, Neil;Herrell, Richard;Lehner, Thomas;Liang, Kung-Yee;Eaves, Lindon;Hoh, Josephine;Griem, Andrea;Kovacs, Maria;Ott, Jurg;Merikangas, Kathleen Ries
在5-羟色胺转运体连接多态区域(5-HTTLPR)和应激性生活事件之间的相互作用增加严重抑郁症风险的报道之后，通过包括环境暴露，大量的资源被投入到识别复杂的精神和行为障碍的候选基因上。利用已发表的数据和个人水平的原始数据，对5-羟色胺转运体基因与抑郁症的应激性生活事件之间的相互作用进行荟萃分析。截至2009年3月，在PubMed、EMBASE和CogcINFO数据库中搜索得到26项研究，其中14项符合荟萃分析的标准。Meta分析的研究标准包括已发表的关于5-HTTLPR基因(SS、SL或LL)、应激性生活事件(0、1、2、≥3)或类似物之间的联系的数据，以及由《精神疾病诊断和统计手册》(第四版)或《国际疾病统计分类第10版》(ICD-10)定义的抑郁症的分类测量，或使用标准评分表中的切点来定义抑郁症。为了最大限度地提高我们使用通用变量定义框架的能力，我们还要求获得2008年前发表的符合纳入标准的所有研究的原始数据。在包括在荟萃分析中的14项研究中，有10项也包括在对原始个人水平数据的第二次性别特定的荟萃分析中。用Logistic回归分析5-HTTLPR短等位基因数、应激性生活事件数及其交互作用对抑郁的影响。分别计算每项研究的优势比(OR)和95%可信区间(CI)，然后利用随机效应荟萃分析获得个体估计的加权平均值。同时进行了性别组合和性别特定的Meta分析。在总共14 250名参与者中，1769人被归类为患有抑郁症，12 481人被归类为没有抑郁症。在对已发表数据的荟萃分析中，应激性生活事件的数量与抑郁显著相关(OR，1.41；95%CI，1.25-1.57)。各单项研究均未发现5-HTTLPR基因与抑郁症的相关性(OR，1.05；95%CI，0.98~1.13)，也未观察到基因型与应激性生活事件对抑郁症的交互作用(OR，1.01；95%CI，0.94~1.10)。在个体水平数据的性别特定的荟萃分析中也发现了类似的结果。这项荟萃分析没有发现证据表明，单独的5-羟色胺转运体基因或与应激性生活事件的相互作用与单独的男性、单独的女性或男女合并患抑郁症的风险增加有关。
Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, ≥3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14 250 participants, 1769 were classified as having depression; 12 481 as not having depression. In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.
登录
查看更多内容
影响因子：
0.9
作者：
Eaves, LJ
通讯作者：
Eaves, LJ
影响因子：
11
作者：
Anguelova, M;Benkelfat, C;Turecki, G
通讯作者：
Turecki, G
影响因子：
56.9
作者：
Caspi, A;McClay, J;Poulton, R
通讯作者：
Poulton, R
影响因子：
30.8
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
通讯作者：
Bertram, Lars
DOI：
10.1073/pnas.0704292104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Caspi, Avshalom;Williams, Benjamin;Moffitt, Terrie E.
通讯作者：
Moffitt, Terrie E.