Date of Award

1-1-2009

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

College of Arts Humanities and Social Sciences, Psychology

First Advisor

Bruce F. Pennington, Ph.D.

Second Advisor

Jan Keenan

Third Advisor

Sarah Watamura

Fourth Advisor

Dick Olson

Fifth Advisor

Erik Willcutt

Keywords

Bioecological, Diathesis-stress, Dyslexia, Gene x environment interactions, Gene by environment interactions, Reading disability

Abstract

The goal of this project was to advance understanding of the complex multifactorial etiology of developmental dyslexia, or reading disability (RD), by investigating gene x environment (G x E) interactions. This project tested for G x E interactions using molecular genetic methods and measures of psychosocial and bioenvironmental risk factors. There are two competing predictions that can be derived from existing G x E models about the expected direction of interactions in RD. There could be "diathesis-stress" interactions in which the effects of genotype are stronger in risk environments, or there could be "bioecological" interactions in which the effects of genotype are stronger in optimal environments. This study was a sib-pair linkage design including dizygotic twins and their non-twin siblings (age 8-19 years) from 212 families. Analyses initially focused on identifying genetic and environmental risk factors showing main effects on reading phenotypes. Sib-pair linkage analyses with two regression-based linkage models (DeFries-Fulker and Haseman-Elston) showed converging evidence for linkage in 4 regions previously associated with RD, 1p36-p34, 3p12-q13, 6p22.2, and 15q21. Across chromosomal locations, the phenotype with the strongest evidence for linkage was rapid naming. In the environmental analyses, three home variables (parental education, books in the home, and child print exposure) and two bioenvironmental variables (prenatal exposure to smoking and birth weight) showed statistically independent main effects on child reading. The G x E analyses were conducted at the significant linkage peaks with the environments showing main effects. Both DeFries-Fulker and Haseman-Elston G x E analyses showed converging evidence for diathesis-stress G x E interaction with parent education at the chromosome 1 and 3 loci for phonological phenotypes. Follow-up analyses controlling for scaling artifacts, G-E correlations, and ADHD comorbidity revealed that the diathesis-stress G x E interactions were generally robust to these confounding factors. Discussion of the results focused on exploration of the diathesis-stress interactions in the context of previous behavioral genetic and molecular genetic findings, including dimensions that may be important for directionality of interactions, such as genetic approach (behavioral versus molecular), sample characteristics (age, disorder, and comorbidity), and environmental range.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Lauren M. McGrath

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

154 p.

Discipline

Clinical Psychology, Genetics

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