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Understanding the Complex Etiologies of Developmental Disorders: Behavioral and Molecular Genetic Approaches

Willcutt, Erik G. PhD*†; Pennington, Bruce F. PhD; Duncan, Laramie MA*†; Smith, Shelley D. PhD§; Keenan, Janice M. PhD; Wadsworth, Sally PhD; DeFries, John C. PhD*†; Olson, Richard K. PhD*†

Journal of Developmental & Behavioral Pediatrics: September 2010 - Volume 31 - Issue 7 - p 533-544
doi: 10.1097/DBP.0b013e3181ef42a1
Special Article

Objective: This article has 2 primary goals. First, a brief tutorial on behavioral and molecular genetic methods is provided for readers without extensive training in these areas. To illustrate the application of these approaches to developmental disorders, etiologically informative studies of reading disability (RD), math disability (MD), and attention-deficit hyperactivity disorder (ADHD) are then reviewed. Implications of the results for these specific disorders and for developmental disabilities as a whole are discussed, and novel directions for future research are highlighted.

Method: Previous family and twin studies of RD, MD, and ADHD are reviewed systematically, and the extensive molecular genetic literatures on each disorder are summarized. To illustrate 4 novel extensions of these etiologically informative approaches, new data are presented from the Colorado Learning Disabilities Research Center, an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders.

Conclusions: RD, MD, and ADHD are familial and heritable, and co-occur more frequently than expected by chance. Molecular genetic studies suggest that all 3 disorders have complex etiologies, with multiple genetic and environmental risk factors each contributing to overall risk for each disorder. Neuropsychological analyses indicate that the 3 disorders are each associated with multiple neuropsychological weaknesses, and initial evidence suggests that comorbidity between the 3 disorders is due to common genetic risk factors that lead to slow processing speed.

From the *Department of Psychology and Neuroscience, University of Colorado at Boulder, Boulder, CO; †Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO; ‡Department of Psychology, University of Denver, Denver, CO; §Medical Genetics Department, University of Nebraska Medical Center, Omaha, NE.

Received March 2010; accepted June 2010.

Primary funding for this research was provided by NICHD Center grant P50 HD 27802. This study was supported by National Institutes of Health grants R01 HD 47264, R01 MH 63207, R01 HD 38526, P50 MH 79485, R01 MH 70037, R01 DA 24002, R01 DC 05190, R0 HD 49027, and T32 HD 07289.

Address for reprints: Erik Willcutt, PhD, Department of Psychology and Neuroscience, UCB 345, University of Colorado, Boulder, Boulder, CO 80309;

© 2010 Lippincott Williams & Wilkins, Inc.