Single-nucleotide variations and linkage disequilibrium patterns in three candidate genes for attention deficit hyperactivity disorder

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Glen Howel G. Acosta (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
David L. Remington

Abstract: "Allelic variations in the genes involving the dopaminergic system, particularly the dopamine transporter (DAT1/SLC6A3), dopamine receptor 4 (DRD4) and Catecol-O-Methyltransferase (COMT) genes have been associated with Attention Deficit Hyperactivity Disorder (AD/HD). However, the results of these studies have been variable and inconclusive in part due to the inconsistencies of experimental and statistical methodologies, phenotypic heterogeneity, low penetrance of the genes implicated, and population stratification. Genetic association studies based on linkage disequilibrium (LD) offer a promising approach to the study of common complex diseases. This study characterized LD patterns in three human populations (CEU, YRI, CHB+JPT) in the three genes mentioned above and identified factors affecting the inconsistencies of genetic association studies in AD/HD. We used the HapMap database and the Haploview program to evaluate linkage disequilibrium patterns of SNPs in these genes. The regression results suggest that there is a trend toward poorer capturing of rare SNPs, which would mean lesser detection of AD/HD associations if rare SNPs were causative on these genes. However, sparse sampling of tag SNPs in these genes (COMT and DAT1/SLC6A3) does not capture the other SNPs well and that a denser tag SNP set is needed to further test our results. The significant reductions of the r2 in the other two populations relative to the CEU supports the contention that associations on these genes varies between populations and suggests that prior assessment of tag SNPs using the HapMap is an essential step in the design of genetic association studies"--from author-supplied metadata.

Additional Information

Publication
Thesis
Language: English
Date: 2009
Keywords
Attention Deficit Hyperactivity Disorder , ADHD, dopaminergic, dopamine, DAT1/SLC6A3, DRD4, Catecol-O-Methyltransferase, COMT, Single-nucleotide, Linkage disequilibrium , genes, allele
Subjects
Attention-deficit hyperactivity disorder $x Genetic aspects.
Attention Deficit Disorder with Hyperactivity $x Genetics $x Children.
Linkage (Genetics)
Dopamine $x Receptors.

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