title: Candidate gene-environment interaction research: reflections and recommendations.
abstract: Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing the 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 (cG×E) 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 cG×E. We review the importance of the measurement of the gene and environment of interest in cG×E studies. We discuss statistical concerns with modeling cG×E that are frequently overlooked. Furthermore, we review other challenges that have likely contributed to the cG×E 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 cG×E studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University ddick@vcu.edu.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.affiliation: Department of Psychiatry, Washington University in St. Louis.
authors.forename: Arpana
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Institute for Behavioral Genetics, University of Colorado Boulder.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keller
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University.
authors.forename: Amy
authors.initials: A
authors.lastname: Adkins
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University.
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.affiliation: Department of Psychology, University of Notre Dame.
authors.forename: Scott
authors.initials: S
authors.lastname: Monroe
authors.affiliation: Department of Psychiatry, Washington University in St. Louis.
authors.forename: John K
authors.initials: JK
authors.lastname: Hewitt
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Department of Psychological Sciences, University of Missouri.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Sher
mesh_terms: D000818:Animals; D059647:Gene-Environment Interaction; D036281:Genetic Research; D006801:Humans; D012107:Research Design
keywords: G×E; candidate genes; genetics; gene–environment interaction