Gene x Environment Interactions at the Serotonin Transporter Locus
Gene x Environment Interactions at the Serotonin Transporter Locus
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DOI：
10.1016/j.biopsych.2008.06.009
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发表时间：
2009-02-01
影响因子：
10.6
通讯作者：
Flint, Jonathan
中科院分区：
文献类型：
--
作者：
Munafo, Marcus R.;Durrant, Caroline;Flint, Jonathan
背景资料：虽然人们普遍认为人类的疾病和行为取决于环境和遗传变异，家庭和双胞胎研究支持的观点，环境与基因相互作用的例子在分子水平上确定（G x E）没有那么好地建立。方法：我们对5-羟色胺转运蛋白进行了系统回顾和荟萃分析，（5-HTTLPR）多态性区域x应激性生活事件（SLE）的文献中，并调查在何种程度上在这篇文献中报道的主要影响是一致的一些G × E假说。我们的目的是提供一个框架，以评估的稳健性的索赔存在的interaction.Results：从我们的系统评价和荟萃分析的结果表明，5-HTTLPR基因型和5 -HTTLPR和SLE之间的相互作用的影响抑郁症的风险的主要影响是可以忽略不计的。我们发现，只有少数的研究报告的复制，是在原来的report.Conclusions质量相当：鉴于合理的假设可能的遗传和环境的影响大小，我们的模拟表明，已发表的研究是动力不足。这一点，连同其他方面的文献，使我们认为，积极的结果为5-HTTLPR x SLE的相互作用在逻辑回归模型是兼容的机会发现。
Background: Although it is universally accepted that human disease and behavior depend upon both environmental and genetic variation, a view supported by family and twin studies, examples of environmental interactions with genes identified at the molecular level (G x E) are not so well established.Methods: We carried out a systematic review and meta-analysis of the serotonin transporte (5-HTTLPR) polymorphic region x stressful life event (SLE) literature and investigated to what extent the main effects reported in this literature are consistent with a number of G x E hypotheses. Our aim was to provide a framework in which to assess the robustness of the claim for the presence of an interaction.Results: The results from our systematic review and meta-analysis indicate that the main effect of 5-HTTLPR genotype and the interaction effect between 5 -HTTLPR and SLE on risk of depression are negligible. We found that only a minority of studies report a replication that is qualitatively comparable to that in the original report.Conclusions: Given reasonable assumptions regarding likely genetic and environmental effect sizes, our simulations indicate that published studies are underpowered. This, together with other aspects of the literature, leads us to suggest that the positive results for the 5-HTTLPR x SLE interactions in logistic regression models are compatible with chance findings.