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Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model

  • Alexia Jolicoeur-Martineau (a1), Jay Belsky (a2), Eszter Szekely (a1) (a3), Keith F. Widaman (a4), Michael Pluess (a5), Celia Greenwood (a1) (a6) and Ashley Wazana (a1) (a3) (a7)...


Currently, two main approaches exist to distinguish differential susceptibility from diathesis-stress and vantage sensitivity in Genotype × Environment interaction (G × E) research: regions of significance (RoS) and competitive-confirmatory approaches. Each is limited by its single-gene/single-environment foci given that most phenotypes are the product of multiple interacting genetic and environmental factors. We thus addressed these two concerns in a recently developed R package (LEGIT) for constructing G × E interaction models with latent genetic and environmental scores using alternating optimization. Herein we test, by means of computer simulation, diverse G × E models in the context of both single and multiple genes and environments. Results indicate that the RoS and competitive-confirmatory approaches were highly accurate when the sample size was large, whereas the latter performed better in small samples and for small effect sizes. The competitive-confirmatory approach generally had good accuracy (a) when effect size was moderate and N ≥ 500 and (b) when effect size was large and N ≥ 250, whereas RoS performed poorly. Computational tools to determine the type of G × E of multiple genes and environments are provided as extensions in our LEGIT R package.


Corresponding author

Author for correspondence: Ashley Wazana, Centre for Child Development and Mental Health, Jewish General Hospital, 4335 Cote Sainte Catherine Road, Montreal, Quebec, H3T 1E4Montreal, Quebec, Canada; E-mail:


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Distinguishing differential susceptibility, diathesis-stress, and vantage sensitivity: Beyond the single gene and environment model

  • Alexia Jolicoeur-Martineau (a1), Jay Belsky (a2), Eszter Szekely (a1) (a3), Keith F. Widaman (a4), Michael Pluess (a5), Celia Greenwood (a1) (a6) and Ashley Wazana (a1) (a3) (a7)...


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