Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression
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Culverhouse, Robert C; Bowes, Lucy; Breslau, Naomi; Nurnberger Jr, John I; Burmeister, Margit; Fergusson, David M; Munafò, Marcus; Saccone, Nancy L; Bierut, Laura J
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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...[Show more]
dc.contributor.author | Culverhouse, Robert C | |
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dc.contributor.author | Bowes, Lucy | |
dc.contributor.author | Breslau, Naomi | |
dc.contributor.author | Nurnberger Jr, John I | |
dc.contributor.author | Burmeister, Margit | |
dc.contributor.author | Fergusson, David M | |
dc.contributor.author | Munafò, Marcus | |
dc.contributor.author | Saccone, Nancy L | |
dc.contributor.author | Bierut, Laura J | |
dc.date.accessioned | 2016-01-06T02:17:43Z | |
dc.date.available | 2016-01-06T02:17:43Z | |
dc.identifier.issn | 1471-244X | |
dc.identifier.uri | http://hdl.handle.net/1885/95289 | |
dc.description.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. | |
dc.description.sponsorship | This work was supported by National Institutes of Health grants R21 DA033827 and R01 DA026911 from the National Institute on Drug Abuse, P01 CA089392 from the National Cancer Institute, and U10 AA008401 from the National Institute on Alcohol Abuse and Alcoholism. | |
dc.publisher | BioMed Central | |
dc.rights | © Culverhouse et al.; licensee BioMed Central Ltd. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | |
dc.source | BMC Psychiatry | |
dc.subject | cooperative behavior | |
dc.subject | depression | |
dc.subject | depressive disorder | |
dc.subject | gene-environment interaction | |
dc.subject | genotype | |
dc.subject | humans | |
dc.subject | life change events | |
dc.subject | research design | |
dc.subject | serotonin plasma membrane transport proteins | |
dc.subject | stress, psychological | |
dc.title | Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 13 | |
dc.date.issued | 2013-11-12 | |
local.identifier.absfor | 060400 | |
local.identifier.ariespublication | u3526593xPUB21 | |
local.publisher.url | http://www.biomedcentral.com/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Culverhouse, Robert C, Washington University School of Medicine, United States of America | |
local.contributor.affiliation | Bowes, Lucy, University of Oxford, United Kingdom | |
local.contributor.affiliation | Breslau, Naomi, Michigan State University, United States of America | |
local.contributor.affiliation | Nurnberger, John I, Indiana University School of Medicine, United States of America | |
local.contributor.affiliation | Easteal, Simon, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University | |
local.contributor.affiliation | Burmeister, Margit, University of Michigan, United States of America | |
local.contributor.affiliation | Fergusson, David M, University of Otago, New Zealand | |
local.contributor.affiliation | Munafo, Marcus, University of Bristol, United Kingdom | |
local.contributor.affiliation | Saccone, Nancy L, Washington University School of Medicine, United States of America | |
local.contributor.affiliation | Bierut, Laura J, Washington University School of Medicine, United States of America | |
local.identifier.essn | 1471-244X | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 304 | |
local.bibliographicCitation.lastpage | 12) | |
local.identifier.doi | 10.1186/1471-244X-13-304 | |
local.identifier.absseo | 920499 | |
dc.date.updated | 2016-06-14T08:54:55Z | |
local.identifier.scopusID | 2-s2.0-84887367513 | |
local.identifier.thomsonID | 000329134900002 | |
Collections | ANU Research Publications |
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