The primary goal of the proposed study is to assess the genetic etiology of reading disability (RD) and comorbid Attention-Deficit/Hyperactivity Disorder (ADHD), the two most prevalent disorders of childhood. To accomplish this goal, an extensive psychometric test battery, including the WISC-IV, tests of reading performance and related cognitive processes, and parent and teacher ratings of ADHD, will be administered to a sample of 1,650 children from 600 families in which at least one of two or more siblings has a school history of reading difficulties. DNA will be isolated from blood or buccal cell samples obtained from all siblings and both biological parents, and each sample will be genotyped using a procedure that provides genotypes for over 10,000 single-nucleotide polymorphisms in a single assay. These extensive phenotypic and genotypic data will be used to accomplish three goals. First, a genome scan will be conducted in the largest sample of sibling pairs ascertained for RD that has been collected to date. This analysis will attempt to replicate the localization of quantitative trait loci (QTLs) for RD that have been reported in previous studies, and is also expected to reveal new QTLs that have not been detected in previous genome scans. Second, bivariate linkage analyses will be employed to conduct the first genome-wide scan for QTLs with pleiotropic effects on RD and ADHD. Finally, exploratory analyses will be conducted to capitalize on other aspects of the rich phenotypic dataset, including a univariate genome-wide scan for DSM-IV ADHD in this enriched sample of siblings ascertained for reading difficulties.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD047264-02
Application #
7095922
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Miller, Brett
Project Start
2005-07-15
Project End
2010-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$553,538
Indirect Cost
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
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Brodsky, Kimberly; Willcutt, Erik G; Davalos, Deana B et al. (2014) Neuropsychological functioning in childhood-onset psychosis and attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry 55:811-8
Eicher, John D; Powers, Natalie R; Miller, Laura L et al. (2014) Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. Hum Genet 133:869-81
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Willcutt, Erik G; Chhabildas, Nomita; Kinnear, Mikaela et al. (2014) The internal and external validity of sluggish cognitive tempo and its relation with DSM-IV ADHD. J Abnorm Child Psychol 42:21-35
Gialluisi, A; Newbury, D F; Wilcutt, E G et al. (2014) Genome-wide screening for DNA variants associated with reading and language traits. Genes Brain Behav 13:686-701
Miller, Amanda C; Keenan, Janice M; Betjemann, Rebecca S et al. (2013) Reading comprehension in children with ADHD: cognitive underpinnings of the centrality deficit. J Abnorm Child Psychol 41:473-83
Willcutt, Erik G; Petrill, Stephen A; Wu, Sarah et al. (2013) Comorbidity between reading disability and math disability: concurrent psychopathology, functional impairment, and neuropsychological functioning. J Learn Disabil 46:500-16
Willcutt, Erik G (2012) The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 9:490-9

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