%0 Journal Article
%T Statistical Genetic Approaches to Investigate Genotype-by-Environment Interaction: Review and Novel Extension of Models.
%A Diego VP
%A Manusov EG
%A Almeida M
%A Laston S
%A Ortiz D
%A Blangero J
%A Williams-Blangero S
%J Genes (Basel)
%V 15
%N 5
%D 2024 04 25
%M 38790175
%F 4.141
%R 10.3390/genes15050547
%X Statistical genetic models of genotype-by-environment (G×E) interaction can be divided into two general classes, one on G×E interaction in response to dichotomous environments (e.g., sex, disease-affection status, or presence/absence of an exposure) and the other in response to continuous environments (e.g., physical activity, nutritional measurements, or continuous socioeconomic measures). Here we develop a novel model to jointly account for dichotomous and continuous environments. We develop the model in terms of a joint genotype-by-sex (for the dichotomous environment) and genotype-by-social determinants of health (SDoH; for the continuous environment). Using this model, we show how a depression variable, as measured by the Beck Depression Inventory-II survey instrument, is not only underlain by genetic effects (as has been reported elsewhere) but is also significantly determined by joint G×Sex and G×SDoH interaction effects. This model has numerous applications leading to potentially transformative research on the genetic and environmental determinants underlying complex diseases.