Novel directions for G × E analysis in psychiatry.

G × E in psychiatry may explain why environmental risk factors have big impact in some individuals but not in others, and conversely why relatives that are genetically at risk for disease do not all develop disease. Here we discuss two novel methods that use an aggregate genome-wide measure of genetic risk to detect G × E and estimate its effect in the population using data currently available and data we anticipate will be available in the near future. The first method exploits summary statistics from large-scale genome-wide association studies ignorant of the environmental conditions and detects G × E in an out-of-sample risk-profiling framework. The second method relies on larger samples and is based on a mixed linear model framework. It estimates variance explained directly from single nucleotide polymorphisms and environmental measures. Both methods have great potential to improve public health interventions focusing on risk-based screening that is informed by both genetic and environmental risk factors.