Dataset Information

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis.

ABSTRACT: INTRODUCTION:Evidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involving FADS2 variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification. METHODS/DESIGN:To clarify how FADS2 and breastfeeding interact in their association with IQ, we are conducting a consortium-based meta-analysis of independent studies. Results produced by each individual study using standardised analysis scripts and harmonised data will be used. INCLUSION CRITERIA:breastfeeding, IQ and either rs174575 or rs1535 polymorphisms available; and being of European ancestry. EXCLUSION CRITERIA:twin studies; only poorly imputed genetic data available; or unavailability of proper ethics approval. Studies will be invited based on being known to have at least some of the required data, or suggested by participating studies as potentially eligible. This inclusive approach will favour achieving a larger sample size and be less prone to publication bias. DISCUSSION:Improving current understanding of FADS2-breastfeeding interaction may provide important biological insights regarding the importance of long-chain polyunsaturated fatty acids for the breastfeeding-IQ association. This meta-analysis will help to improve such knowledge by replicating earlier studies, conducting additional analysis and evaluating different sources of heterogeneity. Publishing this protocol will minimise the possibility of bias due to post hoc changes to the analysis protocol.

SUBMITTER: Hartwig FP

PROVIDER: S-EPMC4916639 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis.

Hartwig Fernando Pires FP Davies Neil Martin NM Horta Bernardo Lessa BL Victora Cesar Gomes CG Davey Smith George G

BMJ open 20160615 6

<h4>Introduction</h4>Evidence from observational studies and randomised controlled trials suggests that breastfeeding is positively associated with IQ, possibly because breast milk is a source of long-chain polyunsaturated fatty acids. Different studies have detected gene-breastfeeding interactions involving FADS2 variants and intelligence. However, findings are inconsistent regarding the direction of such effect modification.<h4>Methods/design</h4>To clarify how FADS2 and breastfeeding interact ...[more]

PMID: 27311901

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Project description:BackgroundDebate 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/designTo 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 criteriaOur 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 sourcesThis 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.DiscussionVariation 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.

Dataset Information

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis.

Publications

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: protocol for a collaborative meta-analysis.

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