Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression

Culverhouse, Robert C., Bowes, Lucy, Breslau, Naomi, Nurnberger, John I. Jr, Burmeister, Margit, Fergusson, David M., Munafo, Marcus, Saccone, Nancy L., Bierut, Laura J., 5-HTTLPR, Stress, and Depression Consortium and Wray, Naomi (2013) Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression. BMC Psychiatry, 13 1-12. doi:10.1186/1471-244X-13-304

Author Culverhouse, Robert C.
Bowes, Lucy
Breslau, Naomi
Nurnberger, John I. Jr
Burmeister, Margit
Fergusson, David M.
Munafo, Marcus
Saccone, Nancy L.
Bierut, Laura J.
5-HTTLPR, Stress, and Depression Consortium
Wray, Naomi
Title Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression
Journal name BMC Psychiatry   Check publisher's open access policy
ISSN 1471-244X
Publication date 2013-11-12
Sub-type Article (original research)
DOI 10.1186/1471-244X-13-304
Open Access Status DOI
Volume 13
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
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Study eligibility criteria: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects.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.

Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article # 304

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 23 Oct 2014, 15:02:07 EST by Debra McMurtrie on behalf of Queensland Brain Institute