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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 …