This article examines Gene × Environment (G × E) interactions in two comorbid developmental disorders-reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD)-as a window on broader issues on G × E interactions in developmental psychology. The authors first briefly review types of G × E interactions, methods for detecting them, and challenges researchers confront in interpreting such interactions. They then review previous evidence for G × E interactions in RD and ADHD, the directions of which are opposite to each other: bioecological for RD and diathesis stress for ADHD. Given these results, the authors formulate and test predictions about G × E interactions that would be expected at the favorable end of each symptom dimension (e.g., aboveaverage reading or attention). Consistent with their prediction, the authors found initial evidence for a resilience interaction for above-average reading: higher heritability in the presence of lower parental education. However, they did not find a G × E interaction at the favorable end of the ADHD symptom dimension. The authors conclude with implications for future research.Correspondence concerning this article should be addressed to Bruce F. Pennington, Department of Psychology, University of Denver, 2155 South Race Street, Denver, CO 80208-0001. bpenning@du.edu. NIH Public Access Author ManuscriptDev Psychol. Author manuscript; available in PMC 2010 January 1. In this article, we review current models of Gene × Environment (G × E) interaction and apply them to two comorbid developmental disorders-reading disability (RD) and attention-deficit/ hyperactivity disorder (ADHD)-and to the favorable ends of their symptom dimensions. These two disorders are good models in which to explore G × E interactions because they are common developmental disorders, with estimates of 5%-10% prevalence in both cases (American Psychiatric Association, 2000; Shaywitz, Shaywitz, Fletcher, & Escobar, 1990), and they both have genetic and environmental components to their etiology. Current behavior genetic analyses estimate the heritability of RD to be about 58% (Pennington & Olson, 2005) and the heritability of ADHD to be about 76% (Faraone et al., 2005). As these estimates show, the influence of genetics in these disorders is quite strong, but the fact that the heritability estimates are not 100% in either disorder leaves room for environmental influences. On the basis of this pattern, it is not too surprising that both disorders show preliminary evidence of G × E interactions.What is intriguing is that this evidence indicates opposite directions for these interactions: RD is more heritable in a favorable environment (a bioecological G × E interaction, which is explained in more detail below), and ADHD is more heritable in a risk environment (the familiar diathesis-stress interaction found in other psychopathologies). This opposite pattern of interactions is important to understand, and we discuss what it may mean. We also test whether this opposite pattern occurs in ...

Background RD and ADHD are comorbid and genetically correlated, especially the inattentive dimension of ADHD (ADHD-I). However, previous research indicates that RD and ADHD enter into opposite gene by environment (GxE) interactions. Methods This study used behavioral genetic methods to replicate these opposite GxE interactions in a sample of same-sex MZ and DZ twin pairs from the Colorado Learning Disabilities Research Center (CLDRC; DeFries et al., 1997) and to test a genetic hypothesis for why these opposite interactions occur. Results We replicated opposite GxE interactions for RD (bioecological) and ADHD-I (diathesis-stress) with parental education in the same sample of participants. The genetic hypothesis for this opposite pattern of interactions is that only genes specific to each disorder enter into these opposite interactions, not the shared genes underlying their comorbidity. To test this hypothesis, we used single models with an exploratory three-way interaction, in which the GxE interactions for each disorder were moderated by comorbidity. Neither three-way interaction was significant. The heritability of RD did not vary as a function of parental education and ADHD-I. Similarly, the heritability of ADHD-I did not vary as a function of parental education and RD. Conclusions We documented opposite GxE interactions in RD and ADHD-I in the same overall twin sample, but the explanation for this apparent paradox remains unclear. Examining specific genes and more specific environmental factors may help resolve the paradox.