Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression
Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression
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DOI：
10.1186/1471-244x-13-304
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发表时间：
2013-11-12
期刊：
影响因子：
4.4
通讯作者：
Bierut, Laura J.
中科院分区：
文献类型：
--
作者：
Culverhouse, Robert C.;Bowes, Lucy;Bierut, Laura J.
背景资料：关于5-羟色胺转运体连锁多态性区域（5-HTTLPR）的变异在抑郁症中起什么作用（如果有的话）的争论正在进行中。一些研究报道了5-HTTLPR变异和影响抑郁风险的压力生活事件之间的相互作用，另一些研究报道了5-HTTLPR变异对抑郁的主要影响，而另一些研究则没有发现主要或相互作用影响的证据。多项研究的荟萃分析也得出了不同的结论。方法/设计：为了提高对5-HTTLPR变异和压力在抑郁症发展中的联合作用的理解，我们正在进行多个独立数据集的荟萃分析。这种协调的方法利用了使用集中开发的标准化脚本进行的新分析。本出版物文件的协议，这一合作，财团为基础的荟萃分析5-HTTLPR的变化，压力，和depression.Study资格标准：我们的目标是邀请所有的数据集，已发表或未发表的，与5-HTTLPR基因型和评估的压力和抑郁症至少300名受试者。数据来源：本项目目前包括来自35个独立小组的研究者，提供至少N = 33，761名参与者的数据。分析计划在开始数据分析之前确定。个体研究数据集的分析将由研究者进行，研究者使用集中开发的标准化分析脚本收集数据，以确保各研究中心的分析方法一致。该联盟作为一个小组将审查和解释的荟萃分析results.Discussion：在5-HTTLPR的变化是假设缓和抑郁症的压力反应。为了检验关于5-HTTLPR变异对抑郁症作用的特定假设，我们将使用先验确定的变量和分析，对从所有可用数据中获得的从头结果进行协调荟萃分析。基于Caspi及其同事2003年关于GxE相互作用的原始报告的主要分析将通过次要分析进行补充，以帮助解释和澄清从效应机制到贡献研究之间异质性的问题。本方案的出版旨在保护该项目免受偏倚报告的影响，并提高读者在完成后解释该特定荟萃分析结果的能力。
Background: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.Methods/Design: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression.Study eligibility criteria: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias.Data sources: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results.Discussion: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.