Editorial Policy for Candidate Gene Studies

Johnston, Charlotte; Lahey, Benjamin B.; Matthys, Walter

doi:10.1007/s10802-013-9741-0

Cited by 30 publications

(27 citation statements)

References 28 publications

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“…Based on these concerns, some leaders of opinion have suggested that a large proportion of significant gene × environment interaction (GEI) findings are in fact false positives [23,260]. This scepticism has been adopted by multiple journals, which have implemented stringent criteria for candidate gene and interaction studies considered for review [270,271]. This portion of the review will focus on issues in GEI studies related to (1) statistical modelling of interaction terms, (2) modelling of confounding variables, (3) timing of environmental exposure across the life span and (4) measurement of predictor and outcome variables.…”

Section: Methodological Considerations In Gene-environment Interactiomentioning

confidence: 99%

The importance of gene–environment interactions in human obesity

2016

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The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

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Section: Methodological Considerations In Gene-environment Interactiomentioning

confidence: 99%

The importance of gene–environment interactions in human obesity

2016

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“…In essence, skeptics are concerned that the lessons learned from high-powered genome-wide association studies, which failed to corroborate previous candidate gene findings (9–13), will apply equally to G×E findings once large genome-wide interaction studies (14) are performed. In response to such concerns, at least two journals, Behavior Genetics (15) and Journal of Abnormal Child Psychology (16), have recently published policies outlining stricter criteria that must be met before manuscripts reporting candidate gene main effects or interactions will be considered for review.…”

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confidence: 99%

Gene × Environment Interaction Studies Have Not Properly Controlled for Potential Confounders: The Problem and the (Simple) Solution

Keller

2014

Biological Psychiatry

577

553

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Candidate gene-by-environment (G×E) interaction research tests the hypothesis that the effects of some environmental variable (e.g., childhood maltreatment) on some outcome measure (e.g., depression) depend on a particular genetic polymorphism. Because this research is inherently non-experimental, investigators have been rightly concerned that detected interactions could be driven by confounders (e.g., ethnicity, gender, age, socioeconomic status, etc.) rather than by the specified genetic or environmental variables per se. In an attempt to eliminate such alternative explanations for detected G×E interactions, investigators routinely enter the potential confounders as covariates in general linear models. However, this practice does not control for the effects these variables might have on the G×E interaction. Rather, to properly control for confounders, researchers need to enter the covariate-by-environment and the covariate-by-gene interaction terms in the same model that tests the G×E term. In this manuscript, I demonstrate this point analytically and show that the practice of improperly controlling for covariates is the norm in the G×E interaction literature to date. Thus, many alternative explanations for G×E findings that investigators had thought were eliminated have not been.

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“…At the forefront of efforts has been the study of behavior genetics. For example, the discipline's leading disciplinary journals (Behavior Genetics; see Hewitt 2012) and journals that routinely publish genetic research (Journal of Abnormal Child Psychology; see Johnston et al 2013) have published policies outlining stricter criteria that manuscripts reporting candidate gene main effects or interactions must meet before they will be considered for peer review. These criteria include the use of multiple statistical methods to evaluate an effect and following up significant cGxE effects with replication attempts in independent samples as well as replication within the same sample.…”

Section: Discussionmentioning

confidence: 99%