Abstract
The insightful overview by Sir Michael Rutter (this issue) on gene–environment interdependence comes about 10 years after the breakthrough Science publications on gene–environment interactions (G×E) involving the MAOA and 5-HTT genes by Caspi et al. (Citation2002, Citation2003). Since then, a field of research has burgeoned that has produced replications as well as intriguing new evidence of gene–environment interdependence. At the same time, however, the field has witnessed a growing scepticism about the relevance of studying gene–environment interactions and has seen replication failures (see Duncan & Keller, Citation2011; Risch et al., Citation2009). Against this backdrop, we comment and elaborate on several of the key issues raised by Rutter, and suggest some directions for future research on G×E. Specifically, we discuss (1) replication issues; (2) the crucial role of experiments in understanding gene–environment interdependence; (3) current unknowns with regard to differential susceptibility; and (4) clinical and practical implications of G×E research.