Abstract
Some Gene × Environment interaction (G×E) research has focused upon single candidate genes, whereas other related work has targeted multiple genes (e.g., polygenic scores). Each approach has informed efforts to identify individuals who are either especially vulnerable to the negative effects of contextual adversity (diathesis stress) or especially susceptible to both positive and negative contextual conditions (differential susceptibility). A critical step in all such molecular G×E research is the selection of genetic variants thought to moderate environmental influences, a subject that has not received a great deal of attention in critiques of G×E research (beyond the observation of small effects of individual genes). Here we conceptually distinguish three phases of G×E work based on the selection of genes presumed to moderate environmental effects and the theoretical basis of such decisions: (a) single candidate genes, (b) composited (multiple) candidate genes, and (c) GWAS-derived polygenic scores. This illustrative, not exhaustive, review makes it clear that implicit or explicit theoretical assumptions inform gene selection in ways that have not been clearly articulated or fully appreciated.
Highlights
Ever since the turn of the century, much attention has been paid to Gene × Environment (G×E) interplay (Rutter, 2006)
The three major phases target (a) single candidate genes and (b) composited candidate genes, sometimes based on the “biological plausibility” that they will be involved in G×E interaction; and (c) polygenic scores based on genome-wide association studies (GWAS)
This study focused on a functional polymorphism in the promoter of the monoamine oxidase A (MAOA) gene to characterize genetic vulnerability to maltreatment because the neurotransmitters just mentioned had all been linked to aggressive behavior in humans and mice (e.g., Cases et al, 1995; Manuck, Flory, Ferrell, Mann, & Muldoon, 2000; Rowe, 2001; Shih & Thompson, 1999), thereby making this gene a “biologically plausible” candidate when investigating G×E interaction and antisocial behavior
Summary
Ever since the turn of the century, much attention has been paid to Gene × Environment (G×E) interplay (Rutter, 2006). Risk alleles In the first (and continuing) phase of G×E research, studies relied on a single candidate gene as a genetic moderator of an environmental effect in predicting, typically, a psychiatric disorder or symptoms of a disorder, including but not limited to antisocial behavior, substance use, and depression.
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