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Gene by environment interactions influencing reading disability and the inattentive symptom dimension of attention deficit/hyperactivity disorder

Rosenberg, Jenni; Pennington, Bruce F; Willcutt, Erik G; Olson, Richard K
BACKGROUND:Reading disability (RD) and attention deficit/hyperactivity disorder (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 (G × E) interactions. METHODS:This study used behavioral genetic methods to replicate these opposite G × E interactions in a sample of same-sex monozygotic and dizygotic 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 G × E 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 G × E 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 G × E 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.
PMCID:3235245
PMID: 21884522
ISSN: 1469-7610
CID: 2898042

Individual prediction of dyslexia by single versus multiple deficit models

Pennington, Bruce F; Santerre-Lemmon, Laura; Rosenberg, Jennifer; MacDonald, Beatriz; Boada, Richard; Friend, Angela; Leopold, Daniel R; Samuelsson, Stefan; Byrne, Brian; Willcutt, Erik G; Olson, Richard K
The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia--two single-deficit models, two multiple-deficit models, and one hybrid model--in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individual's level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.
PMCID:3270218
PMID: 22022952
ISSN: 1939-1846
CID: 2898052

Gene X environment interactions in reading disability and attention-deficit/hyperactivity disorder

Pennington, Bruce F; McGrath, Lauren M; Rosenberg, Jenni; Barnard, Holly; Smith, Shelley D; Willcutt, Erik G; Friend, Angela; Defries, John C; Olson, Richard K
This article examines Gene x Environment (G x E) interactions in two comorbid developmental disorders--reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD)--as a window on broader issues on G x E interactions in developmental psychology. The authors first briefly review types of G x E interactions, methods for detecting them, and challenges researchers confront in interpreting such interactions. They then review previous evidence for G x 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 x E interactions that would be expected at the favorable end of each symptom dimension (e.g., above-average 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 x E interaction at the favorable end of the ADHD symptom dimension. The authors conclude with implications for future research.
PMCID:2743891
PMID: 19209992
ISSN: 0012-1649
CID: 2898032