Candidate gene-environment interaction research: reflections and recommendations.
Danielle M. Dick,Arpana Agrawal,Matthew C. Keller,Amy E. Adkins,Fazil Aliev,Scott M. Monroe,John K. Hewitt,Kenneth S. Kendler,Kenneth J. Sher +8 more
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TLDR
Recommendations are provided for rigorous research practices for cG×E studies that are believed to advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.Abstract:
Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing our understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cGxE) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cGxE. We review the importance of the measurement of the gene and environment of interest in cGxE studies. We discuss statistical concerns with modeling cGxE that are frequently overlooked. And we review other challenges that have likely contributed to the cGxE literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cGxE studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.read more
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No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples.
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TL;DR: The results suggest that early hypotheses about depression candidate genes were incorrect and that the large number of associations reported in the depression candidate gene literature are likely to be false positives.
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Developmental Adaptation to Stress: An Evolutionary Perspective.
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References
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Book
Multiple Regression: Testing and Interpreting Interactions
Leona S. Aiken,Stephen G. West +1 more
TL;DR: In this article, the effects of predictor scaling on the coefficients of regression equations are investigated. But, they focus mainly on the effect of predictors scaling on coefficients of regressions.
Journal ArticleDOI
Multiple Regression: Testing and Interpreting Interactions
TL;DR: In this article, multiple regression is used to test and interpret multiple regression interactions in the context of multiple-agent networks. But it is not suitable for single-agent systems, as discussed in this paper.
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,Karen Sugden,Terrie E. Moffitt,Alan Taylor,Ian W. Craig,Hona Lee Harrington,Joseph L. McClay,Jonathan Mill,Judy Martin,Antony W. Braithwaite,Richie Poulton +10 more
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Katherine S. Button,John P. A. Ioannidis,Claire Mokrysz,Brian A. Nosek,Jonathan Flint,Emma S J Robinson,Marcus R. Munafò +6 more
TL;DR: It is shown that the average statistical power of studies in the neurosciences is very low, and the consequences include overestimates of effect size and low reproducibility of results.
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